Biology subjects

Barnes, G.

Publications and source records attributed to Barnes, G..

15 recordsLinked to original sources

bioRxiv2026

Intracranial Validation of Magnetoencephalography Across Oscillatory Frequency and Depth

Non-invasive, whole-brain neuroimaging methods such as functional magnetic resonance imaging, electroencephalography (EEG), and magnetoencephalography (MEG) are essential tools for studying the basis of human cognition in health and disease. MEG offers the opportunity to study neural activity at its intrinsic timescale, by recording the magnetic fields generated by electrical currents within the brain from outside the skull. Moreover, recently developed optically pumped magnetometers (OPMs) allow these recordings to take place in new settings, for example during naturalistic behaviour and in previously inaccessible populations. These breakthroughs have led to a shift in the neuroimaging landscape, with a global increase in the adoption of MEG. Crucially, however, the extent to which MEG recordings can measure different features of neural activity remains unclear. To address this issue, we leveraged a unique and rare dataset of concurrent MEG and intracranial EEG recordings from a cohort of epileptic patients. We found that group-level inferences of spontaneous oscillatory dynamics made with source-localised MEG, i.e. estimates of power and bursts, accurately reflected the underlying neural activity. As expected, the agreement was strongest for lower-frequency activity (delta, theta, and alpha) and superficial sources, and weakest in the gamma range. Crucially, however, MEG was also sensitive to deep structures: it captured oscillatory power and burst dynamics in the hippocampus, most robustly in the theta band. These findings demonstrate that MEG is sensitive to physiologically meaningful activity in cortical and subcortical regions and establish a foundation for the interpretation of future MEG studies across a wide range of research domains.

neuroscience↗

bioRxiv2026

Forward Modelling for Magnetospinography: Systematic Comparison of Boundary Element and Finite Element Methods

Magnetospinography (MSG) enables non-invasive measurement of spinal cord electrophysiology, but accurate interpretation of these signals depends critically on forward modelling assumptions. We compared four vertebral bone representations: continuous, homogeneous-toroidal, inhomogeneous-toroidal, and MRI-derived-realistic, implemented within both boundary element method (BEM) and finite element method (FEM) frameworks. Lead-fields were computed across the full spinal cord for three orthogonal source orientations. When comparing matched model pairs, BEM and FEM produced consistent forward solutions, with median relative errors below 3.1% and median squared correlation coefficients exceeding 0.998 across all bone geometries. Vertebral bone geometry exerted a systematic and orientation-dependent influence on predicted lead fields. The dominant distinction was between continuous and segmented bone representations rather than between simplified and anatomically detailed segmented models. For left-right oriented sources, segmented geometries produced substantially higher field amplitudes (fT/nAm) than the continuous model throughout the cord (35-72%), while toroidal and MRI-derived realistic models produced comparable results across both frameworks, with median r2 exceeding 0.97 between segmented models compared to 0.67-0.85 for continuous versus segmented comparisons. Sensor placement further modulated sensitivity profiles, with posterior arrays exhibiting greater sensitivity lower down the cord, but anterior and posterior sensors showing comparable sensitivity in the cervical region.

neuroscience↗

bioRxiv2026

An integrated virtual reality platform for naturalistic neuroimaging with magnetoencephalography

Studying the brain in motion promises deep insights into the neural circuits that support complex, real-world behaviour. In humans, wearable optically pumped magnetometers (OPMs) enable magnetoencephalography (MEG) with millisecond temporal resolution and millimetre spatial precision during movement. Integrating this technology with virtual reality (VR) could enable fully naturalistic experimental paradigms, but magnetic interference from existing head-mounted displays (HMDs) prevents reliable whole-brain MEG recordings. Here, we present and validate a VR system that integrates with wearable, OPM-based MEG. At its core is a purpose-designed HMD with minimal ferromagnetic material, resulting in magnetic flux density two orders of magnitude lower than consumer-grade alternatives at comparable resolution and weight. Using phantom measurements and established perceptual and cognitive benchmark tasks across participants, we demonstrate robust stimulus-induced neuronal activity at both sensor and source level. Crucially, these sources span the entire brain, including visual, motor and prefrontal cortices, as well as hippocampus. Our proposed VR system is straightforward to produce, readily extendable, and enables whole-brain MEG during immersive, naturalistic behaviours.

neuroscience↗

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.

neuroscience↗

bioRxiv2025

Copper acquisition in Bacillus subtilis involves Cu(II) exchange between YcnI and YcnJ

The transition metal copper is biologically essential across all three domains of life. Several copper-dependent proteins and enzymes produced by the Gram-positive bacterium Bacillus subtilis have been characterized. However, many questions remain about how copper is recognized and trafficked to metalate cuproproteins. The ycnKJI operon in B. subtilis encodes a suite of proteins implicated in copper uptake and regulation, including the copper-binding protein YcnI and the putative copper importer YcnJ. Here, we demonstrate that one of the extracellular domains within YcnJ (YcnJCopC) binds Cu(II) in 1:1 stoichiometry with high affinity using a histidine brace motif. Biochemical results reveal that YcnJCopC and YcnI can exchange Cu(II). Genetic studies reveal that loss of either YcnI or YcnJ, or mutation of the key residues required for Cu(II)-binding, leads to a growth defect under conditions of copper limitation. Together, these data suggest that the Cu(II)-binding sites in both YcnI and YcnJ contribute to efficient import under Cu limited conditions. Our results support a model in which YcnI may sequester Cu(II) from YcnJ, serving a regulatory role to limit the amount of copper that enters the cytoplasm and allowing Cu(II) to be stored for later import in the outer face of the membrane. This transfer of Cu(II) between extracellular domains of membrane-bound proteins represents a potential new paradigm in bacterial copper usage.

biochemistry↗

bioRxiv2025

Distorting anatomy to test MEG models and metrics

Current flow that gives rise to non-invasive Magnetoencephalographic (MEG) data derives predominantly from pyramidal neurons oriented orthogonal to the cortical surface. The estimate of current flow based on extra-cranial magnetic fields is a well-known ill-posed problem; however, this current distribution must depend on anatomy. In other words, a veridical estimate of current flow should discriminate between true and distorted versions of the brain. Here, we make use of advances in diffeomorphic brain shape modelling to construct a set of parametrically deformable cortical surfaces. We use a latent space of 100 components to construct cortical surfaces that are representative of the population. We show how these geometric distortions can be used to quantify the performance of MEG source reconstruction algorithms and metrics of fit.

neuroscience↗

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.

neuroscience↗

bioRxiv2024

Large-Scale Motor Dynamics Associated with Reaching are Altered in Essential Tremor

Essential Tremor (ET) is a very common neurological disorder characterised by involuntary rhythmic movements attributable to pathological synchronization within corticothalamic circuits. Previous work has focused on tremor in isolation, overlooking broader disturbances to motor control during naturalistic movements such as reaching. We hypothesised that ET disrupts the sequential engagement of large-scale rhythmic brain networks, leading to both tremor and deficits in motor planning and execution. To test this, we performed whole-head neuroimaging during an upper-limb reaching task using high-density electroencephalography in ET patients and healthy controls, alongside optically pumped magnetoencephalography in a smaller cohort. Key motor regions--including the supplementary motor area, premotor cortex, posterior parietal cortex, and motor cerebellum--were synchronized to tremor rhythms. Patients exhibited a 15% increase in low beta (14-21 Hz) desynchronization over the supplementary motor area during movement, which strongly correlating with tremor severity (R2 = 0.85). A novel dimensionality reduction technique revealed four distinct networks accounting for 97% of the variance in motor-related brain-wide oscillations, with ET altering their sequential engagement. Consistent with our hypothesis, the frontoparietal beta network- normally involved in motor planning-exhibited additional desynchronization during movement execution in ET patients. This altered engagement correlated with slower movement velocities, suggesting an adaptation towards feedback-driven motor control. These findings reveal fundamental disruptions in distributed motor control networks in ET and identify novel biomarkers as targets for next-generation brain stimulation therapies.

neuroscience↗

bioRxiv2023

Interdependence of a microtubule polymerase and a motor protein in establishment of kinetochore end-on attachments

Faithful segregation of chromosomes into daughter cells during mitosis requires formation of attachments between kinetochores and mitotic spindle microtubules. Chromosome alignment on the mitotic spindle, also referred to as congression, is facilitated by translocation of side-bound chromosomes along the microtubule surface, which allows the establishment of end-on attachment of kinetochores to microtubule plus ends. Spatial and temporal constraints hinder observation of these events in live cells. Therefore, we used our previously developed reconstitution assay to observe dynamics of kinetochores, the yeast kinesin-8, Kip3, and the microtubule polymerase, Stu2, in lysates prepared from metaphase-arrested budding yeast, Saccharomyces cerevisiae. Using total internal reflection fluorescence (TIRF) microscopy to observe kinetochore translocation on the lateral microtubule surface toward the microtubule plus end, motility was shown to be dependent on both Kip3, as we reported previously, and Stu2. These proteins were shown to have distinct dynamics on the microtubule. Kip3 is highly processive and moves faster than the kinetochore. Stu2 tracks both growing and shrinking microtubule ends but also colocalizes with moving lattice-bound kinetochores. In cells, we observed that both Kip3 and Stu2 are important for establishing chromosome biorientation, Moreover, when both proteins are absent, biorientation is completely defective. All cells lacking both Kip3 and Stu2 had declustered kinetochores and about half also had at least one unattached kinetochore. Our evidence argues that despite differences in their dynamics, Kip3 and Stu2 share roles in chromosome congression to facilitate proper kinetochore-microtubule attachment.

cell biology↗

bioRxiv2022

Stimulating microtubule growth is not the essential function of the microtubule polymerase Stu2

ch-TOG family proteins, including the budding yeast Stu2, are essential for spindle formation and chromosome segregation. Such functions depend on an array of activities ranging from microtubule nucleation, polymerization and depolymerization, to conferring tension sensitivity to kinetochores. This functional diversity makes it challenging to dissect these various functions and understand their relative importance. Here, we developed separation-of-function mutants and used artificial tethering tools to elucidate several important mechanistic insights into Stu2s essential role. We show that Stu2s microtubule polymerization activity depends on its basic linker region but is surprisingly dispensable for viability; that in fact, Stu2 carries out an essential kinetochore-associated function; and finally, that Stu2s precise location within the kinetochore is critical for its function, suggesting a spatial separation mode of action may underlie its ability to confer tension sensitivity. Our findings highlight the significance of Stu2s kinetochore role and provide insights into the molecular mechanisms by which it performs its various functions.

cell biology↗

bioRxiv2022

Cik1 and Vik1 Accessory Proteins Confer Distinct Functions to the Kinesin-14, Kar3

The budding yeast Saccharomyces cerevisiae has a closed mitosis in which the mitotic spindle and cytoplasmic microtubules (MTs) used to segregate chromosomes remain separated by the nuclear envelope throughout the cell cycle. Kar3, the yeast kinesin-14, has unique roles in both compartments and has been implicated in capturing unattached kinetochores, stabilizing crosslinked interpolar microtubules (MT), and creating intranuclear and cytoplasmic MT arrays at the spindle pole body for kinetochore capture and karyogamy, respectively. Here, we show that two proteins, Cik1 and Vik1, that form heterodimers with Kar3, regulate its localization and function within the cell and along MTs in a cell cycle-dependent manner. Using a cell cycle synchronized, yeast MT dynamics reconstitution assay in cell lysate, we found that Kar3Vik1 induces MT catastrophes in S phase and metaphase and limits MT polymerization in G1 and anaphase. In contrast, Kar3Cik1 is a catastrophe and pause promoter in G1, while increasing catastrophes in metaphase and anaphase. Adapting this assay to track single-molecules, we saw that Kar3Cik1 is necessary for tracking MT plus-ends in S phase and metaphase, but, surprisingly, not during anaphase. These experiments demonstrate how the binding partners of Kar3 modulate its diverse functions both spatially and temporally. SUMMARY STATEMENTWe show through biochemical reconstitution experiments and live-cell imaging that the functions and localization of the budding yeast kinesin-14, Kar3, are dictated by which of its two accessory protein binding partners, Cik1 or Vik1, it binds to and by the cell cycle stage.

cell biology↗

bioRxiv2022

Reconstitution of Kinetochore and Microtubule Dynamics Reveals a Role for a Kinesin-8 in Establishing End-on Attachments

During mitosis, individual microtubules make attachments to chromosomes via a specialized protein complex called the kinetochore to faithfully segregate the chromosomes to daughter cells. Translocation of kinetochores on the lateral surface of the microtubule has been proposed to contribute to high fidelity chromosome capture and alignment at the mitotic midzone, but has been difficult to observe in vivo because of spatial and temporal constraints. To overcome these barriers, we used total internal reflection fluorescence (TIRF) microscopy to track the interactions between endogenously tagged tubulin, kinetochore proteins, and other microtubule-associated proteins in lysates from metaphase-arrested Saccharomyces cerevisiae. Using both TIRF microscopy and cryo-correlative light microscopy and electron tomography, we successfully reconstituted microtubule-bound, intact kinetochores. These kinetochores translocate on the lateral microtubule surface toward the microtubule plus end and transition to end-on attachment, whereupon microtubule depolymerization commences. The directional kinetochore movement is dependent on the highly processive kinesin-8, Kip3. We propose that Kip3 facilitates stable kinetochore attachment to microtubule plus ends through its abilities to move the kinetochore laterally on the surface of the microtubule and to regulate microtubule plus end dynamics.

cell biology↗

bioRxiv2018

Motor cortical beta transients delay movement initiation and track errors

Motor cortical activity in the beta range (13-30 Hz) is a hallmark signature of healthy and pathological movement, but its behavioural relevance remains unclear. Recent work in primates and human sensory cortex suggests that sustained oscillatory beta activity observed on average, may arise from the summation of underlying short-lasting, high-amplitude bursts of activity. Classical human movement-related event-related beta desynchronisation (ERD) and synchronization (ERS) may thus provide insufficient, non-dynamic, summaries of underlying focal spatio-temporal burst activity, limiting insight into their functional role during healthy and pathological movement.\n\nHere we directly investigate this transient beta burst activity and its putative behavioural relevance for movement control, using high-precision magnetoencephalography (MEG). We quantified the subject-specific (n=8), trial-wise (n>12,000) dynamics of beta bursts, before and after movement. We show that beta activity on individual trials is dominated by high amplitude, short lasting bursts. While average beta changes generally manifest as bilaterally distributed activity (FWHM = 25mm), individual bursts are spatially more focal (FWHM = 6 mm), sporadic (1.3 -1.5/s), and transient (mean: 96 ms).\n\nPrior to movement (the period of the classical ERD), the timing of the last pre-movement burst predicts movement onset, suggesting a role in the specification of the goal of movement. After movement (the period of the classical ERS), the first beta burst is delayed by ~100ms after a response error occurs, intimating a role in error monitoring and evaluation.\n\nMovement-related beta activity is therefore dominated by a spatially dispersed summation of short lasting, sporadic and focal bursts. Movement-related beta bursts coordinate the retrieval and updating of movement goals in the pre- and post-movement periods, respectively.

neuroscience↗

bioRxiv2018

Neural competitive queuing of ordinal structure underlies skilled sequential action

The fluent retrieval and production of movement sequences is essential for a variety of daily activities such as speech, tool-use, musical and athletic performance, but the neural mechanisms underlying sequence planning remain elusive. Here, participants learned sequences of finger presses with different timings and different finger orders, and reproduced them in a magneto-encephalography (MEG) scanner. We classified the MEG patterns immediately preceding each press in the sequence, and examined their dynamics over the production of the whole sequence. Our results confirm a role for the competitive queuing of upcoming action representations in the production of learned motor sequences, extending previous computational and non-human primate recording studies to non-invasive measures in humans. In addition, we show that competitive queuing does not simply reflect specific motor actions, but representations of higher-level sequential order that generalise across different motor sequences. Finally, we show that the quality of competitive queuing predicts participants production accuracy, and originates from parahippocampal and cerebellar sources. These results suggest that the brain learns and produces multiple behavioural sequences by flexibly combining representations of specific actions with more abstract, parallel representations of sequential structure.

neuroscience↗

bioRxiv2018

Quantifying the performance of MEG source reconstruction using resting state data

Resting state networks measured with magnetoencephalography (MEG) form transiently stable spatio-temporal patterns in the subsecond range, and therefore fluctuate more rapidly than previously appreciated. These states populate and interact across the whole brain, are simple to record, and possess the same dynamic structure of task related changes. They therefore provide a generic, heterogeneous, and plentiful functional substrate against which to test different MEG recording and reconstruction approaches. Here we validate a non-invasive method for quantifying the resolution of different inversion assumptions under different recording regimes (with and without head-casts) based on resting state MEG. Spatio-temporally partitioning of data into self-similar periods confirmed a rich and rapidly dynamic temporal structure with a small number of regularly reoccurring states. To test the anatomical precision that could be resolved through these transient states we then inverted these data onto libraries of systematically distorted, subject specific, cortical meshes and compared the quality of the fit using Cross Validation and a Free Energy metric. This revealed which inversion scheme was able to best support the least distorted (most accurate) anatomical models. Both datasets showed an increase in model fit as anatomical models moved towards the true cortical surface. In the head-cast MEG data, the Empirical Bayesian Beamformer (EBB) algorithm showed the best mean anatomical discrimination (3.7 mm) compared with Minimum Norm / LORETA (6.0 mm) and Multiple Sparse priors (9.4 mm). This pattern was replicated in the second (conventional dataset) although with a marginally poorer prediction of the missing (cross-validated) data. Our findings suggest that the abundant resting state data now commonly available could be used to refine and validate MEG source reconstruction methods or recording paradigms.

neuroscience↗