Biology subjects

McEvoy, A. W.

Publications and source records attributed to McEvoy, A. W..

5 recordsLinked to original sources

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

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↗

bioRxiv2024

The inflammatory micro-environment induced by targeted CNS radiotherapy is underpinned by disruption of DNA methylation

Although targeted radiotherapy (RT) is integral to the increasing survival of cancer patients, it has significant side-effects, the cellular and molecular mechanisms of which are not fully understood. During RT epigenetic changes occur in neoplastic tissue, but few studies have assessed these in non-neoplastic tissue and results are highly variable. Using bulk DNA methylation and RNA sequencing as well as spatial transcriptomics (ST) in a unique cohort of patient tissue samples, we show distinct differences in DNA methylation patterns in irradiated brain tissue, whilst ST characterisation identifies specific micro-environmental niches present after irradiation and highlights neuropeptides that could be propagating neuroinflammation. We also show that in a cerebral organoid (CO) model of early changes in neurons after irradiation there are similar DNA methylation alterations and disruption of the DNA methylation machinery, suggesting that early but persistent epigenetic dysregulation plays a role in neurotoxicity. We provide a link between radiotherapy induced neuroinflammation and disruption of DNA methylation for the first time and suggest possible driving mechanisms for this chronic neuroinflammation.

neuroscience↗

bioRxiv2019

Node abnormality predicts seizure outcome and relates to long-term relapse after epilepsy surgery

ObjectiveWe assessed pre-operative structural brain networks and clinical characteristics of patients with drug resistant temporal lobe epilepsy (TLE) to identify correlates of post-surgical seizure outcome at 1 year and seizure relapses up to 5 years.\n\nMethodsWe retrospectively examined data from 51 TLE patients who underwent anterior temporal lobe resection (ATLR) and 29 healthy controls. For each patient, using the pre-operative structural, diffusion, and post-operative structural MRI, we generated two networks: pre-surgery network and surgically-spared network. The pre-surgery network is the whole-brain network before surgery and the surgically-spared network is a subnetwork of the pre-surgery network which is expected to remain unaffected by surgery and hence present post-operatively. Standardising these networks with respect to controls, we determined the number of abnormal nodes before surgery and expected to remain after surgery. We incorporated these 2 abnormality measures and 13 commonly acquired clinical data from each patient in a robust machine learning framework to estimate patient-specific chances of seizures persisting after surgery.\n\nResultsPatients with more abnormal nodes had lower chance of seizure freedom at 1 year and even if seizure free at 1 year, were more likely to relapse within five years. In the surgically-spared networks of poor outcome patients, the number of abnormal nodes was greater and their locations more widespread than in good outcome patients. We achieved 0.84 {+/-} 0.06 AUC and 0.89 {+/-} 0.09 specificity in detecting unsuccessful seizure outcomes at 1-year. Moreover, the model-predicted likelihood of seizure relapse was significantly correlated with the grade of surgical outcome at year-one and associated with relapses up-to five years post-surgery.\n\nConclusionNode abnormality offers a personalised non-invasive marker, that can be combined with clinical data, to better estimate the chances of seizure freedom at 1 year, and subsequent relapse up to 5 years after ATLR.

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↗