arXiv subjects

Peter N Taylor

Publications and source records attributed to Peter N Taylor.

15 recordsLinked to original sources

arXiv2024

Diminished circadian and ultradian rhythms of human brain activity in pathological tissue in vivo

Chronobiological rhythms, such as the circadian rhythm, have long been linked to neurological disorders, but it is currently unknown how pathological processes affect the expression of biological rhythms in the brain. Here, we use the unique opportunity of long-term, continuous intracranially recorded EEG from 38 patients (totalling 6338 hours) to delineate circadian (daily) and ultradian (minute to hourly) rhythms in different brain regions. We show that functional circadian and ultradian rhythms are diminished in pathological tissue, independent of regional variations. We further demonstrate that these diminished rhythms are persistent in time, regardless of load or occurrence of pathological events. These findings provide evidence that brain pathology is functionally associated with persistently diminished chronobiological rhythms in vivo in humans, independent of regional variations or pathological events. Future work interacting with, and restoring, these modulatory chronobiological rhythms may allow for novel therapies.

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arXiv2023

Complementary structural and functional abnormalities to localise epileptogenic tissue

When investigating suitability for surgery, people with drug-refractory focal epilepsy may have intracranial EEG (iEEG) electrodes implanted to localise seizure onset. Diffusion-weighted magnetic resonance imaging (dMRI) may be acquired to identify key white matter tracts for surgical avoidance. Here, we investigate whether structural connectivity abnormalities, inferred from dMRI, may be used in conjunction with functional iEEG abnormalities to aid localisation and resection of the epileptogenic zone (EZ), and improve surgical outcomes in epilepsy. We retrospectively investigated data from 43 patients with epilepsy who had surgery following iEEG. Twenty five patients (58%) were free from disabling seizures (ILAE 1 or 2) at one year. For all patients, T1-weighted and diffusion-weighted MRIs were acquired prior to iEEG implantation. Interictal iEEG functional, and dMRI structural connectivity abnormalities were quantified by comparison to a normative map and healthy controls respectively. First, we explored whether the resection of maximal (dMRI and iEEG) abnormalities related to improved surgical outcomes. Second, we investigated whether the modalities provided complementary information for improved prediction of surgical outcome. Third, we suggest how dMRI abnormalities may be useful to inform the placement of iEEG electrodes as part of the pre-surgical evaluation using a patient case study. Seizure freedom was 15 times more likely in those patients with resection of maximal dMRI and iEEG abnormalities (p=0.008). Both modalities were separately able to distinguish patient outcome groups and when combined, a decision tree correctly separated 36 out of 43 (84%) patients based on surgical outcome. Structural dMRI could be used in pre-surgical evaluations, particularly when localisation of the EZ is uncertain, to inform personalised iEEG implantation and resection.

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arXiv2023

Aperiodic MEG abnormality in patients with focal to bilateral tonic-clonic seizures

Aperiodic activity is a physiologically distinct component of the electrophysiological power spectrum. It is suggested to reflect the balance of excitation and inhibition in the brain, within selected frequency bands. However, the impact of recurrent seizures on aperiodic activity remains unknown, particularly in patients with severe bilateral seizures. Here, we hypothesised greater aperiodic abnormality in the epileptogenic zone, in patients with focal to bilateral tonic clonic (FBTC) seizures, and earlier age of seizure onset. Pre-operative magnetoencephalography (MEG) recordings were acquired from 36 patients who achieved complete seizure freedom (Engel I outcome) post-surgical resection. A normative whole brain map of the aperiodic exponent was computed by averaging across subjects for each region in the hemisphere contralateral to the side of resection. Selected regions of interest were then tested for abnormality using deviations from the normative map in terms of z-scores. Resection masks drawn from postoperative structural imaging were used as an approximation of the epileptogenic zone. Patients with FBTC seizures had greater abnormality compared to patients with focal onset seizures alone in the resection volume (p=0.003, area under the ROC curve = 0.78 ). Earlier age of seizure onset was correlated with greater abnormality of the aperiodic exponent in the resection volume (correlation coefficient = -0.3, p= 0.04)) as well as the whole cortex (rho = -0.33, p=0.03). The abnormality of the aperiodic exponent did not significantly differ between the resected and non-resected regions of the brain. Abnormalities in aperiodic components relate to important clinical characteristics such as severity and age of seizure onset. This suggests the potential use of the aperiodic band power component as a marker for severity of epilepsy.

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arXiv2023

Normative brain mapping using scalp EEG and potential clinical application

A normative electrographic activity map could be a powerful resource to understand normal brain function and identify abnormal activity. Here, we present a normative brain map using scalp EEG in terms of relative band power. In this exploratory study we investigate its temporal stability, its similarity to other imaging modalities, and explore a potential clinical application. We constructed scalp EEG normative maps of brain dynamics from 17 healthy controls using source-localised resting-state scalp recordings. We then correlated these maps with those acquired from MEG and intracranial EEG to investigate their similarity. Lastly, we use the normative maps to lateralise abnormal regions in epilepsy. Spatial patterns of band powers were broadly consistent with previous literature and stable across recordings. Scalp EEG normative maps were most similar to other modalities in the alpha band, and relatively similar across most bands. Towards a clinical application in epilepsy, we found abnormal temporal regions ipsilateral to the epileptogenic hemisphere. Scalp EEG relative band power normative maps are spatially stable across time, in keeping with MEG and intracranial EEG results. Normative mapping is feasible and may be potentially clinically useful in epilepsy. Future studies with larger sample sizes and high-density EEG are now required for validation.

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arXiv2023

Temporal stability of intracranial EEG abnormality maps for localising epileptogenic tissue

Objective: Identifying abnormalities in interictal intracranial EEG, by comparing patient data to a normative map, has shown promise for the localisation of epileptogenic tissue and prediction of outcome. The approach typically uses short interictal segments of around one minute. However, the temporal stability of findings has not been established. Methods: Here, we generated a normative map of iEEG in non-pathological brain tissue from 249 patients. We computed regional band power abnormalities in a separate cohort of 39 patients for the duration of their monitoring period (0.92-8.62 days of iEEG data, mean 4.58 days per patient, over 4,800 hours recording). To assess the localising value of band power abnormality, we computed DRS - a measure of how different the surgically resected and spared tissue were in terms of band power abnormalities - over time. Results: In each patient, band power abnormality was relatively consistent over time. The median DRS of the entire recording period separated seizure free (ILAE = 1) and not seizure free (ILAE > 1) patients well (AUC = 0.69). This effect was similar interictally (AUC = 0.69) and peri-ictally (AUC = 0.71). Significance: Our results suggest that band power abnormality DRS, as a predictor of outcomes from epilepsy surgery, is a relatively robust metric over time. These findings add further support for abnormality mapping of neurophysiology data during presurgical evaluation.

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arXiv2022

Effects of anterior temporal lobe resection on cortical morphology

Anterior temporal lobe resection (ATLR) is a surgical procedure to treat drug-resistant temporal lobe epilepsy (TLE). Resection may involve large amounts of cortical tissue. Here, we examine the effects of this surgery on cortical morphology measured in independent variables both near the resection and remotely. We studied 101 individuals with TLE (55 left, 46 right onset) who underwent ATLR. For each individual we considered one pre-surgical MRI and one follow-up MRI 2 to 13 months after surgery. We used our newly developed surface-based method to locally compute traditional morphological variables (average cortical thickness, exposed surface area, and total surface area), and the independent measures $K$, $I$, and $S$, where $K$ measures white matter tension, $I$ captures isometric scaling, and $S$ contains the remaining information about cortical shape. Data from 924 healthy controls was included to account for healthy ageing effects occurring during scans. A SurfStat random field theory clustering approach assessed changes across the cortex caused by ATLR. Compared to preoperative data, surgery had marked effects on all morphological measures. Ipsilateral effects were located in the orbitofrontal and inferior frontal gyri, the pre- and postcentral gyri and supramarginal gyrus, and the lateral occipital gyrus and lingual cortex. Contralateral effects were in the lateral occipital gyrus, and inferior frontal gyrus and frontal pole. The restructuring following ATLR is reflected in widespread morphological changes, mainly in regions near the resection, but also remotely in regions that are structurally connected to the anterior temporal lobe. The causes could include mechanical effects, Wallerian degeneration, or compensatory plasticity. The study of independent measures revealed additional effects compared to traditional measures.

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arXiv2022

Normative brain mapping of interictal intracranial EEG to localise epileptogenic tissue

The identification of abnormal electrographic activity is important in a wide range of neurological disorders, including epilepsy for localising epileptogenic tissue. However, this identification may be challenging during non-seizure (interictal) periods, especially if abnormalities are subtle compared to the repertoire of possible healthy brain dynamics. Here, we investigate if such interictal abnormalities become more salient by quantitatively accounting for the range of healthy brain dynamics in a location-specific manner. To this end, we constructed a normative map of brain dynamics, in terms of relative band power, from interictal intracranial recordings from 234 subjects (21,598 electrode contacts). We then compared interictal recordings from 62 patients with epilepsy to the normative map to identify abnormal regions. We hypothesised that if the most abnormal regions were spared by surgery, then patients would be more likely to experience continued seizures post-operatively. We first confirmed that the spatial variations of band power in the normative map across brain regions were consistent with healthy variations reported in the literature. Second, when accounting for the normative variations, regions which were spared by surgery were more abnormal than those resected only in patients with persistent post-operative seizures (t=-3.6, p=0.0003), confirming our hypothesis. Third, we found that this effect discriminated patient outcomes (AUC=0.75 p=0.0003). Normative mapping is a well-established practice in neuroscientific research. Our study suggests that this approach is feasible to detect interictal abnormalities in intracranial EEG, and of potential clinical value to identify pathological tissue in epilepsy. Finally, we make our normative intracranial map publicly available to facilitate future investigations in epilepsy and beyond.

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arXiv2021

Fluctuations in EEG band power at subject-specific timescales over minutes to days explain changes in seizure evolutions

Epilepsy is recognised as a dynamic disease, where both seizure susceptibility and seizure characteristics themselves change over time. Specifically, we recently quantified the variable electrographic spatio-temporal seizure evolutions that exist within individual patients. This variability appears to follow subject-specific circadian, or longer, timescale modulations. It is therefore important to know whether continuously-recorded interictal iEEG features can capture signatures of these modulations over different timescales. In this work, we analyse continuous intracranial electroencephalographic (iEEG) recordings from video-telemetry units and find fluctuations in iEEG band power over timescales ranging from minutes up to twelve days. As expected and in agreement with previous studies, we find that all subjects show a circadian fluctuation in their iEEG band power. We additionally find other fluctuations of similar magnitude on subject-specific timescales. Importantly, we find that a combination of these fluctuations on different timescales can explain changes in seizure evolutions in most subjects above chance level. These results suggest that subject-specific fluctuations in iEEG band power over timescales of minutes to days may serve as markers of seizure modulating processes. We hope that future work can link these detected fluctuations to their biological driver(s). There is a critical need to better understand seizure modulating processes, as this will enable the development of novel treatment strategies that could minimise the seizure spread, duration, or severity and therefore the clinical impact of seizures.

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arXiv2020

Reliability and comparability of human brain structural covariance networks

Structural covariance analysis is a widely used structural MRI analysis method which characterises the co-relations of morphology between brain regions over a group of subjects. To our knowledge, little has been investigated in terms of the comparability of results between different data sets or the reliability of results over the same subjects in different rescan sessions, image resolutions, or FreeSurfer versions. In terms of comparability, our results show substantial differences in the structural covariance matrix between data sets of age- and sex-matched healthy human adults. These differences persist after site correction, they are exacerbated by low sample sizes, and they are most pronounced when using average cortical thickness as a morphological measure. Down-stream graph theoretic analyses further show statistically significant differences. In terms of reliability, substantial differences were also found when comparing repeated scan sessions of the same subjects, and image resolutions and FreeSurfer versions of the same image. We could further estimate the relative measurement error and showed that it is largest when using thickness. With simulated data, we argue that cortical thickness is least reliable because of larger relative measurement errors. Practically, we make the following recommendations (1) pooling subjects across sites into one group should be avoided, particularly if sites differ in image resolutions, demographics, or preprocessing; (2) surface area and volume should be preferred as morphological measures over cortical thickness; (3) a large number of subjects should be used to estimate structural covariance; (4) measurement error should be assessed where repeated measurements are available; (5) if combining sites is critical, univariate site-correction is insufficient, but error covariance should be explicitly measured and modelled.

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arXiv2020

Band power modulation through intracranial EEG stimulation and its cross-session consistency

Background: Direct electrical stimulation of the brain through intracranial electrodes is currently used to probe the epileptic brain as part of pre-surgical evaluation, and it is also being considered for therapeutic treatments through neuromodulation. It is still unknown, however, how consistent intracranial direct electrical stimulation responses are across sessions, to allow effective neuromodulation design. Objective: To investigate the cross-session consistency of the electrophysiological effect of electrical stimulation delivered through intracranial EEG. Methods: We analysed data from 79 epilepsy patients implanted with intracranial EEG who underwent brain stimulation as part of a memory experiment. We quantified the effect of stimulation in terms of band power modulation and compared this effect from session to session. As a reference, we applied the same measures during baseline periods. Results: In most sessions, the effect of stimulation on band power could not be distinguished from baseline fluctuations of band power. Stimulation effect was also not consistent across sessions; only a third of the session pairs had a higher consistency than the baseline standards. Cross-session consistency is mainly associated with the strength of positive stimulation effects, and it also tends to be higher when the baseline conditions are more similar between sessions. Conclusion: These findings can inform our practices for designing neuromodulation with greater efficacy when using direct electrical brain stimulation as a therapeutic treatment.

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arXiv2020

Independent components of human brain morphology

Quantification of brain morphology has become an important cornerstone in understanding brain structure. Measures of cortical morphology such as thickness and surface area are frequently used to compare groups of subjects or characterise longitudinal changes. However, such measures are often treated as independent from each other. A recently described scaling law, derived from a statistical physics model of cortical folding, demonstrates that there is a tight covariance between three commonly used cortical morphology measures: cortical thickness, total surface area, and exposed surface area. We show that assuming the independence of cortical morphology measures can hide features and potentially lead to misinterpretations. Using the scaling law, we account for the covariance between cortical morphology measures and derive novel independent measures of cortical morphology. By applying these new measures, we show that new information can be gained; in our example we show that distinct morphological alterations underlie healthy ageing compared to temporal lobe epilepsy, even on the coarse level of a whole hemisphere. We thus provide a conceptual framework for characterising cortical morphology in a statistically valid and interpretable manner, based on theoretical reasoning about the shape of the cortex.

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arXiv2019

Carbogen inhalation during Non-Convulsive Status Epilepticus: A quantitative analysis of EEG recordings

Objective: To quantify the effect of inhaled 5% carbon-dioxide/95% oxygen on EEG recordings from patients in non-convulsive status epilepticus (NCSE). Methods: Five children of mixed aetiology in NCSE were given high flow of inhaled carbogen (5% carbon dioxide/95% oxygen) using a face mask for maximum 120s. EEG was recorded concurrently in all patients. The effects of inhaled carbogen on patient EEG recordings were investigated using band-power, functional connectivity and graph theory measures. Carbogen effect was quantified by measuring effect size (Cohen's d) between "before", "during" and "after" carbogen delivery states. Results: Carbogen's apparent effect on EEG band-power and network metrics across all patients for "before-during" and "before-after" inhalation comparisons was inconsistent across the five patients. Conclusion: The changes in different measures suggest a potentially non-homogeneous effect of carbogen on the patients' EEG. Different aetiology and duration of the inhalation may underlie these non-homogeneous effects. Tuning the carbogen parameters (such as ratio between CO2 and O2, duration of inhalation) on a personalised basis may improve seizure suppression in future.

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arXiv2018

The impact of epilepsy surgery on the structural connectome and its relation to outcome

Temporal lobe surgical resection brings seizure remission in up to 80% of patients, with long-term complete seizure freedom in 41%. However, it is unclear how surgery impacts on the structural white matter network, and how the network changes relate to seizure outcome. We used white matter fibre tractography on preoperative diffusion MRI to generate a structural white matter network, and postoperative T1-weighted MRI to retrospectively infer the impact of surgical resection on this network. We then applied graph theory and machine learning to investigate the properties of change between the preoperative and predicted postoperative networks. Temporal lobe surgery had a modest impact on global network efficiency, despite the disruption caused. This was due to alternative shortest paths in the network leading to widespread increases in betweenness centrality post-surgery. Measurements of network change could retrospectively predict seizure outcomes with 79% accuracy and 65% specificity, which is twice as high as the empirical distribution. Fifteen connections which changed due to surgery were identified as useful for prediction of outcome, eight of which connected to the ipsilateral temporal pole. Our results suggest that the use of network change metrics may have clinical value for predicting seizure outcome. This approach could be used to prospectively predict outcomes given a suggested resection mask using preoperative data only.

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arXiv2017

Mechanisms underlying different onset patterns of focal seizures

Focal seizures are episodes of pathological brain activity that appear to arise from a localised area of the brain. The onset patterns of focal seizure activity have been studied intensively, and they have largely been distinguished into two types - low amplitude fast oscillations (LAF), or high amplitude spikes (HAS). Here we explore whether these two patterns arise from fundamentally different mechanisms. Here, we use a previously established computational model of neocortical tissue, and validate it as an adequate model using clinical recordings of focal seizures. We then reproduce the two onset patterns in their most defining properties and investigate the possible mechanisms underlying the different focal seizure onset patterns in the model. We show that the two patterns are associated with different mechanisms at the spatial scale of a single ECoG electrode. The LAF onset is initiated by independent patches of localised activity, which slowly invade the surrounding tissue and coalesce over time. In contrast, the HAS onset is a global, systemic transition to a coexisting seizure state triggered by a local event. We find that such a global transition is enabled by an increase in the excitability of the "healthy" surrounding tissue, which by itself does not generate seizures, but can support seizure activity when incited. In our simulations, the difference in surrounding tissue excitability also offers a simple explanation of the clinically reported difference in surgical outcomes. Finally, we demonstrate in the model how changes in tissue excitability could be elucidated, in principle, using active stimulation. Taken together, our modelling results suggest that the excitability of the tissue surrounding the seizure core may play a determining role in the seizure onset pattern, as well as in the surgical outcome.

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arXiv2017

Understanding Epileptiform After-Discharges as Rhythmic Oscillatory Transients

Electro-cortical activity in patients with epilepsy may show abnormal rhythmic transients in response to stimulation. Even when using the same stimulation parameters in the same patient, wide variability in the duration of transient response has been reported. These transients have long been considered important for the mapping of the excitability levels in the epileptic brain but their dynamic mechanism is still not well understood. To understand the occurrence of abnormal transients dynamically, we use a thalamo-cortical neural population model of epileptic spike-wave activity and study the interaction between slow and fast subsystems. In a reduced version of the thalamo-cortical model, slow wave oscillations arise from a fold of cycles (FoC) bifurcation. This marks the onset of a region of bistability between a high amplitude oscillatory rhythm and the background state. In vicinity of the bistability in parameter space, the model has excitable dynamics, showing prolonged rhythmic transients in response to suprathreshold pulse stimulation. We analyse the state space geometry of the bistable and excitable states, and find that the rhythmic transient arises when the impending FoC bifurcation deforms the state space and creates an area of locally reduced attraction to the fixed point. This area essentially allows trajectories to dwell there before escaping to the stable steady state, thus creating rhythmic transients. In the full thalamo-cortical model, we find a similar FoC bifurcation structure. Based on the analysis, we propose an explanation of why stimulation induced epileptiform activity may vary between trials, and predict how the variability could be related to ongoing oscillatory background activity.

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