Biology subjects

Bush, D.

Publications and source records attributed to Bush, D..

17 recordsLinked to original sources

bioRxiv2026

Firing rate adaptation in grid cells produces macroscopic hexadirectional modulation

Hexadirectional modulation (HexMod) of macroscopic neural activity by movement direction is widely used to measure grid cell activity in human neuroimaging, but its neuronal origin is unclear. Two mechanisms have been proposed: conjunctive gridxdirection cells whose preferred directions align with the grid axes, and firing rate adaptation, which reduces firing when grid fields are visited in quick succession during movement along grid axes. Analysing almost 4,000 grid cells from foraging rats, we found that conjunctive cells' directional tuning was broad and unaligned with grid axes, whereas firing was reduced shortly after grid field visits, consistent with firing rate adaptation. Simulations of realistic grid cell populations demonstrate HexMod with the typical trajectories of human experiments, and show how it depends on grid scale, adaptation time constant, movement speed, and controlling for variation with location. We show firing rate adaptation provides a plausible mechanism for HexMod and a framework for relating human neuroimaging to neuronal activity.

neuroscience↗

bioRxiv2026

Human Hippocampal Theta-Gamma Phase-Amplitude Coupling Signals the Distance to Remembered Goals

In mammals, flexible navigation is believed to rely on a cognitive map of known locations supported by the hippocampus and surrounding medial temporal lobe structures. Hippocampal place cells typically exhibit spatial firing fields within a given environment. Moreover, their firing is modulated by the movement-related theta rhythm such that "theta sweeps" of place cell activity encode the trajectory towards a hidden reward location during goal-directed navigation. Here, we attempted to detect signatures of theta sweeps in the human hippocampal local field potential (LFP) recorded with intracranial EEG. Specifically, we hypothesised that sequences of locations along a planned trajectory encoded by distinct cell assemblies are associated with gamma activity at successive theta phases. To test this hypothesis, we asked N=9 patients with epilepsy to perform a spatial navigation task in desktop virtual reality while we recorded LFP signals from depth electrode contacts implanted across the medial temporal lobe. Consistent with our predictions, we found an increase in hippocampal theta-gamma phase-amplitude coupling, a decrease in gamma power, and theta phase precession of gamma activity as hidden goal locations were approached and the sequence of locations remaining to be traversed became shorter. This suggests that goal-directed hippocampal theta sweeps during navigation are reflected in LFP theta-gamma phase-amplitude coupling, and that these neural mechanisms of model-based planning are conserved across species.

neuroscience↗

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

Ocean acidification changes diet effects and differentially impacts two populations of red abalone (Haliotis rufescens)

Absorption of CO2 by global oceans is decreasing pH resulting in ocean acidification (OA). Impacts on shellfish have been documented in ecologically and commercially important species. We examined the influence of diet and OA between two populations of red abalone (Haliotis rufescens) a species of aquaculture importance and declining wild populations. Populations experience different exposure histories: strong upwelling (Van Damme, California [VD]) historically exposed to low-pH conditions and weak-intermittent upwelling (Santa Barbara, California [SB]). Abalone were cultured under control-pH or OA-conditions and fed crustose coralline algae (CCA) or diatoms used in aquaculture. We tested treatment effects of population, settlement diet, and OA-exposure on survival as influenced by larval-energy stores. Survival in both populations was enhanced by CCA when cultured under both treatment conditions; however, by later stages, this effect remained only for SB. SB had reduced post-settlement survival when cultured under OA-conditions, whereas post-settlement survival of VD was not. Diet affected the relationship between larval-energy and post-settlement survival; a positive relationship when fed diatoms and a negative relationship with CCA. The relationship between larval energy and post-settlement survival was stronger in VD. CCA enhanced juvenile growth in SB cultured abalone at both three-months and one-year post-settlement. Settlement diets can reduce the impacts of OA on early-life stages of abalone, but population differences driven by underlying energetics affect the consistency of this outcome. These findings illuminate the impacts from OA, suggesting populations may be at risk, and inform strategies for developing and sustaining shellfish aquaculture in the face of changing ocean conditions.

physiology↗

bioRxiv2026

Theta phase and theta-gamma coupling organise the spoken language network

Speech production requires rapid coordination of conceptual and lexical processes across distributed cortical networks, yet the neurophysiological mechanisms enabling this coordination remain poorly understood. Oscillatory coupling has emerged as a candidate mechanism for coordinating neural activity across spatial scales. Here, we used whole-head magnetoencephalography during overt picture naming to test how phase and phase-amplitude coupling organise neural dynamics preceding articulation. We show that theta (4-8 Hz) phase coupling increases within two functionally distinct networks: a ventral occipito-temporal network supporting object recognition and a medial fronto-temporal network supporting semantic-lexical retrieval. These networks converged in the right fusiform gyrus beyond chance levels, identifying a candidate integration hub. In parallel, whole-brain analysis of theta-gamma (4-8 Hz, 40-100 Hz) phase-amplitude coupling revealed selective increases in the left inferior frontal and fusiform gyri during picture naming relative to control. Mixed-effects modelling further showed that coupling in the left fusiform correlates with trial-level response times during naming but not control trials. Together, these findings reveal the oscillatory mechanisms that implement known functional specialisation in the spoken language network; theta phase coupling coordinates distributed recognition and retrieval streams, while theta-gamma coupling modulates local computations within core word production nodes. By defining an oscillatory framework for real-time speech production, this work advances mechanistic understanding of the spoken language network and identifies frequency- and region-specific targets for neuromodulation of language production disorders. HighlightsO_LIDistinct oscillatory mechanisms support distributed and local language production processes C_LIO_LITheta phase-coupling distinguishes object recognition and word retrieval networks C_LIO_LITheta-gamma coupling increases locally in core language regions C_LIO_LIIncreases in theta-gamma coupling scale with trial-by-trial naming speed C_LI

neuroscience↗

bioRxiv2026

Fast-ripples are emergent properties of neuronal networks

Fast-ripples (250-500 Hz) have been proposed as a promising biomarker in epilepsy, but their specificity remains unclear. In particular, it is uncertain whether they reflect chance coincident neural activity or distinctly generated pathological entities. We combined in silico simulations, neuronal cultures, the intra-hippocampal kainate rat model of hippocampal epilepsy, and human microwire recordings to investigate whether fast-ripples occur more frequently than expected by the chance aggregation of action potentials. Our simulations showed that chance aggregation can generate fast-ripples and that their incidence changes depending on brain state, an observation that we confirmed in our rodent data. The likelihood of exceeding chance depended on biological system complexity and vigilance state: fast-ripples in neuronal cultures did not surpass chance levels, whereas those in awake - but not sleeping - rodents did. Similarly, the incidence of fast-ripples in awake human recordings was ~30% greater than expected by chance. As such, our findings suggest that most fast-ripples reflect stochastic network activity rather than distinctly generated pathological entities. This work does not rule out FRs as potential indicators of epileptogenic tissue, but it does challenge prevailing assumptions about their generation and specificity. Their higher prevalence in epileptogenic tissue is likely primarily due to increased excitation and/or neural synchronization, rather than peculiar abnormalities in network behavior.

neuroscience↗

bioRxiv2026

Impaired Associative Memory, Inference, and Theta Dynamics in Postictal Psychosis of Epilepsy

Postictal psychosis (PIP) is a severe complication occurring in 2% of people with epilepsy (PWE) whose underlying pathophysiology remains poorly understood. Although historically considered separate from other forms of psychosis, newer evidence demonstrates a shared genetic susceptibility. People with schizophrenia are typically impaired at both associative learning and inferring connections between overlapping associations. Successful associative encoding, retrieval, and inference can each be predicted by changes in frontotemporal theta band activity, which is impaired in rodent models and people with schizophrenia. Here, we recorded high-density scalp EEG from PWE with history of PIP and well-matched control participants while they undertook a memory inference task. We found that associative memory and inference were both impaired in the PIP group, despite no difference in item recognition. Moreover, we found disrupted theta activity during memory encoding and the retrieval of inferred associations in PWE with PIP that likely originated from the medial temporal and frontal lobes. These results suggest a pattern of behavioural deficits and altered neural dynamics common to both PIP and schizophrenia. Interpreted in conjunction with previous genetic studies, they may reflect shared neural mechanisms contributing to psychopathology in both conditions and argue that PIP is a model of more general psychoses.

neuroscience↗

bioRxiv2026

Non-invasive tracking of hippocampal theta oscillations

Hippocampal theta oscillations play a crucial role in the formation of episodic memories by binding multisensory information into coherent episodes. Brain stimulation studies suggest that memory performance can be modulated by targeting these oscillations, offering a potential way of treating memory disorders. However, to effectively engage these rhythms, precise knowledge about their presence, frequency, phase and location is required, which has been a challenge, particularly for non-invasive methods such as magnetoencephalography (MEG). Here, we first asked if hippocampal signals are detectable in MEG recordings. Using simultaneous MEG-intracranial EEG (iEEG) data, we show that invasively recorded hippocampal activity is reflected in MEG sensor signals, demonstrating the feasibility of detecting deep-brain activity non-invasively. Building on this, we introduce a MEG-based analysis pipeline to track hippocampal theta frequency over time. Applied across three independent datasets, the pipeline captured characteristic hippocampal theta frequency patterns in both rodents and humans, and MEG-derived hippocampal frequencies were consistent with those observed simultaneously in intracranial EEG. These findings provide evidence that MEG can reliably track individual hippocampal oscillatory dynamics, paving the way for future non-invasive closed-loop interventions that adapt stimulation frequency and timing to ongoing oscillations.

neuroscience↗

bioRxiv2024

Human Hippocampal Theta Oscillations Organise Distance to Goal Coding

The rodent hippocampal local field potential is dominated by 6-12 Hz theta oscillations during active behaviour that are strongly implicated in spatial coding and memory function across species. Invasive electrophysiology in both rodents and humans has shown increases in hippocampal theta power immediately before the onset of translational movement that persists throughout subsequent motion, and the magnitude of this increase correlates with the distance subsequently travelled. Using non-invasive magnetoencephalography (MEG) and an abstract navigation task, we observed increased theta power during both spatial planning and subsequent navigation. Importantly, theta power in the right hippocampus covaried with subsequent path distance during planning, only when participants were aware of the distance to their goal. During subsequent navigation, hippocampal theta power decreased dynamically as participants approached the goal, only when they were aware of how far they still needed to travel. In addition, theta phase during navigation modulated 70-140 Hz fast gamma amplitude in the entorhinal cortex while traversing novel paths; and 30-70 Hz slow gamma amplitude in the right hippocampus while traversing previously experienced paths. In both cases, theta-gamma phase-amplitude coupling increased with proximity to the goal during navigation, consistent with the hypothesis that sequences of upcoming locations were represented by gamma bursts occurring at successive theta phases. In sum, these findings are consistent with the proposed role of hippocampal theta oscillation in flexible planning and goal-directed spatial navigation across mammalian species.

neuroscience↗

bioRxiv2024

Dynamical Modulation of Hippocampal Replay Sequences through Firing Rate Adaptation

During periods of immobility and sleep, the hippocampus generates diverse self-sustaining sequences of "replay" activity, exhibiting stationary, diffusive, and super-diffusive dynamical patterns. However, the neural mechanisms underlying this diversity in hippocampal sequential dynamics remain largely unknown. Here, we propose such a mechanism demonstrating that modulation of firing rate adaptation in a continuous attractor model of place cells causes the emergence of different types of replay. Our model makes several key predictions. First, more diffusive replay sequences positively correlate with longer theta sequences across animals (both reflecting stronger adaptation). Second, replay diffusivity varies within an animal across behavioural states that affect adaptation (such as wake and sleep). Third, increases in neural excitability, incorporated with firing rate adaptation, reduce the step size of decoded movements within individual replay sequences. We provide new experimental evidence for all three predictions. These insights suggested that the diverse replay dynamics observed in the hippocampus can be reconciled through a simple yet effective neural mechanism, shedding light on its role in hippocampal-dependent cognitive functions and its relationship to other aspects of hippocampal electrophysiology.

neuroscience↗

bioRxiv2022

Firing rate adaptation in continuous attractor neural networks accounts for theta phase shift of hippocampal place cells

Hippocampal place cells in freely moving rodents display both theta phase precession and procession, which is thought to play important roles in cognition, but the neural mechanism for producing theta phase shift remains largely unknown. Here we show that firing rate adaptation within a continuous attractor neural network causes the neural activity bump to oscillate around the external input, resembling theta sweeps of decoded position during locomotion. These forward and backward sweeps naturally account for theta phase precession and procession of individual neurons, respectively. By tuning the adaptation strength, our model explains the difference between "bimodal cells" showing interleaved phase precession and procession, and "unimodal cells" in which phase precession predominates. Our model also explains the constant cycling of theta sweeps along different arms in a T-maze environment, the speed modulation of place cells firing frequency, and the continued phase shift after transient silencing of the hippocampus. We hope that this study will aid an understanding of the neural mechanism supporting theta phase coding in the brain.

neuroscience↗

bioRxiv2021

Ripple Band Phase Precession of Place Cell Firing during Replay

Phase coding offers several theoretical advantages for information transmission compared to an equivalent rate code. Phase coding is shown by place cells in the rodent hippocampal formation, which fire at progressively earlier phases of the movement related 6-12Hz theta rhythm as their spatial receptive fields are traversed. Importantly, however, phase coding is independent of carrier frequency, and so we asked whether it might also be exhibited by place cells during 150-250Hz ripple band activity, when they are thought to replay information to neocortex. We demonstrate that place cells which fire multiple spikes during candidate replay events do so at progressively earlier ripple phases, and that spikes fired across all replay events exhibit a negative relationship between decoded location within the firing field and ripple phase. These results provide insights into the mechanisms underlying phase coding and place cell replay, as well as the neural code propagated to downstream neurons.

neuroscience↗

bioRxiv2019

Theta power and theta-gamma coupling support spatial memory retrieval

Hippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations during spatial memory function, and how this relates to subsequent behaviour. Here we asked ten human epilepsy patients undergoing intracranial EEG recording to perform a desk-top virtual reality spatial memory task, and found that increased theta power in two discrete bands ( low 2-5Hz and high 6-9Hz) during cued retrieval was associated with improved task performance. Similarly, increased coupling between low theta phase and gamma amplitude during the same period was associated with improved task performance. These results support a role of theta oscillations and theta-gamma phase-amplitude coupling in human spatial memory function.

neuroscience↗

bioRxiv2019

Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

Altered neural dynamics in medial prefrontal cortex (mPFC) and hippocampus may contribute to cognitive impairments in the complex chromosomal disorder, Down Syndrome (DS). Here, we demonstrate non-overlapping behavioural differences associated with distinct abnormalities in hippocampal and mPFC electrophysiology during a canonical spatial memory task in three partially trisomic mouse models of DS (Dp1Tyb, Dp10Yey, Dp17Yey) that together cover all regions of homology with human chromosome 21 (Hsa21). Dp1Tyb mice showed slower decision-making (unrelated to the gene dose of DYRK1A, which has been implicated in DS cognitive dysfunction) and altered theta dynamics (reduced frequency, increased hippocampal-mPFC coherence, increased modulation of hippocampal high gamma); Dp10Yey mice showed impaired alternation performance and reduced theta modulation of hippocampal low gamma; while Dp17Yey mice were no different from wildtype mice. These results link specific hippocampal and mPFC circuit dysfunctions to cognitive deficits in DS models and, importantly, map them to discrete regions of Hsa21.

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

Spectral fingerprints or spectral tilt? Evidence for distinct oscillatory signatures of memory formation

Decreases in low frequency power (2-30 Hz) alongside high frequency power increases (>40 Hz) have been demonstrated to predict successful memory formation. Parsimoniously this change in the frequency spectrum can be explained by one factor, a change in the tilt of the power spectrum (from steep to flat) indicating engaged brain regions. A competing view is that the change in the power spectrum contains several distinct brain oscillatory fingerprints, each serving different computations. Here, we contrast these two theories in a parallel MEG-intracranial EEG study where healthy participants and epilepsy patients, respectively, studied either familiar verbal material, or unfamiliar faces. We investigated whether modulations in specific frequency bands can be dissociated in time, space and by experimental manipulation. Both, MEG and iEEG data, show that decreases in alpha/beta power specifically predicted the encoding of words, but not faces, whereas increases in gamma power and decreases in theta power predicted memory formation irrespective of material. Critically, these different oscillatory signatures of memory encoding were evident in different brain regions. Moreover, high frequency gamma power increases occurred significantly earlier compared to low frequency theta power decreases. These results speak against a \"spectral tilt\" and demonstrate that brain oscillations in different frequency bands serve different functions for memory encoding.

neuroscience↗

bioRxiv2018

Human hippocampal theta oscillations reflect sequential dependencies during spatial planning.

Movement-related theta oscillations in rodent hippocampus coordinate forward sweeps of location-specific neural activity that could be used to evaluate spatial trajectories online. This raises the possibility that increases in human hippocampal theta power accompany the evaluation of upcoming spatial choices. To test this hypothesis, we measured neural oscillations during a spatial planning task that closely resembles a perceptual decision-making paradigm. In this task, participants searched visually for the shortest path between a start and goal location in novel mazes that contained multiple choice points, and were subsequently asked to make a spatial decision at one of those choice points. We observed ~4-8 Hz hippocampal/medial temporal lobe theta power increases specific to sequential planning that were negatively correlated with subsequent decision speed, where decision speed was inversely correlated with choice accuracy. These results implicate the hippocampal theta rhythm in decision tree search during planning in novel environments.

neuroscience↗