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Peter N. Taylor

Publications and source records attributed to Peter N. Taylor.

At least 19 recordsLinked to original sources

Habitual lifestyle timing explains circadian timing, but daily lifestyle changes do not, in free-living humans across 2000 days

Background: Both between- and within-subject variations in circadian timing matter for health. If lifestyle changes could be used to regulate circadian timing, they would offer accessible and scalable routes to chronotherapy, but this link remains unclear under real-life conditions. Here, we explore how lifestyle 'traits' (such as typical wake time) and 'states' (day-to-day deviations from traits, such as waking up later than typical) explain between- and within-subject variation in acrophase (peak time) of the circadian rhythm of heart rate (CRHR). Methods: We collected free-living wearable data (smartwatch, continuous glucose monitor) from healthy volunteers for up to 4 weeks. The CRHR was derived from activity-adjusted heart rate, and acrophase was defined as time-of-day at daily CRHR peak. Sleep, food, and physical activity 'factors' were calculated and split into traits and states. Using a linear mixed-effects model, we tested how traits and states associate with between- and within-subject acrophase variance. Findings: Data from 105 healthy volunteers (66 female, age = 42.5 $\pm$ 15.7 years) spanning ~2000 days (18.8 $\pm$ 8.30 days each) were analysed. Traits were substantially more influential than states, explaining 42.3% versus 0.9% of total acrophase variance. Accordingly, traits explained 86.5% of between-subject variance, whereas states explained only 1.8% of within-subject variance. Sleep, food and physical activity factors contributed both jointly and uniquely, and lifestyle timing mattered most. Interpretation: Between-subject lifestyle traits explained acrophase better than within-subject lifestyle states. This asymmetry, alongside the considerable overlap between factors, supports sustained, holistic, timing-focused lifestyle adjustments as chronotherapy targets, testable through future interventional studies.

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Open diffusion MRI and connectivity data for epilepsy and surgery: The IDEAS II release

Epileptic seizures are generated in cerebral networks that propagate ictal and interictal activity. The structure of cerebral networks underpinning epileptic activity can be inferred from diffusion-weighted MRI (DWI). However, publicly available DWI data in individuals with epilepsy are scarce, and processing is technically challenging due to scan-specific artifacts, limiting research progress. Here, we release raw DWI data from 216 individuals with epilepsy and 98 healthy controls. Subject identifiers align with our previous data release (IDEAS), which includes T1-weighted and FLAIR MRI, surgical details, and long-term seizure outcomes after surgery. Preprocessing reduced distortions and artifacts, while fully processed data include diffusion metric maps in native and template space. We also provide parcellated structural connectomes using multiple atlases and connectivity measures. To illustrate the utility of this IDEAS II data, we replicated ENIGMA consortium findings, observing widespread reductions of fractional anisotropy, particularly ipsilateral to the area of seizure onset. We further demonstrate localised abnormality, and network connectivity using streamline tractography in a patient who subsequently underwent temporal lobe resection. This open dataset offers a comprehensive resource to advance research on structural connectivity and surgical outcomes in epilepsy.

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Normative Modelling in Neuroimaging: A Practical Guide for Researchers

Normative modelling is an increasingly common statistical technique in neuroimaging that estimates population-level benchmarks in brain structure. It enables the quantification of individual deviations from expected distributions whilst accounting for biological and technical covariates without requiring large, matched control groups. This makes it a powerful alternative to traditional case-control studies for identifying brain structural alterations associated with pathology. Despite the availability of numerous modelling approaches and several toolboxes with pre-trained models, the distinct strengths and limitations of normative modelling make it difficult to determine how and when to implement them appropriately. This review offers practical guidance and outlines statistical considerations for clinical researchers using normative modelling in neuroimaging. Through a worked example using clinical epilepsy data, we outline considerations for responsible implementation of pre-trained normative models, to support their broad and rigorous adoption in neuroimaging research.

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Anti-seizure medication load is not correlated with early termination of seizure spread

Objective: Anti-seizure medications (ASMs) are the mainstay of treatment for epilepsy, yet their effect on seizure spread is not fully understood. Higher ASM doses have been associated with shorter and less severe seizures. We aimed to test if this effect was due to limiting seizure spread through early termination of otherwise unchanged seizures. Methods: We retrospectively examined intracranial EEG (iEEG) recordings in 15 subjects who underwent ASM tapering during pre-surgical monitoring. We estimated ASM plasma concentrations based on pharmaco-kinetic modeling. In each subject, we identified seizures that followed the same onset and initial spread patterns, but some seizures terminated early (truncated seizures), and other seizures continued to spread (continuing seizures). We first compared seizure duration to ASM concentration for all seizures and the subset of seizures included in truncated-continuing pairs. Then we compared durations of the matched truncated and continuing seizures. Finally, we compared ASM concentrations at the times of truncated seizures and continuing seizures. Results: Seizure durations were found to be significantly longer at lower ASM concentrations. Continuing seizures were significantly longer in duration than matched truncated seizures. We found no substantial difference between ASM concentrations when truncated vs. continuing seizures occurred. Significance: The lack of difference between ASM concentrations at the time of truncated vs. continuing seizures implies a separate mechanism for shortening the duration of seizures beyond stopping the spread pathways early. Additionally, the mechanism causing seizures to be truncated remains unclear. Further research is needed to understand how ASM may modulate seizure duration and severity.

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From Bedside to Desktop: A Data Protocol for Normative Intracranial EEG and Abnormality Mapping

Normative mapping is a framework used to map population-level features of health-related variables. It is widely used in neuroscience research, but the literature lacks established protocols in modalities that do not support healthy control measurements, such as intracranial EEG (icEEG). An icEEG normative map would allow researchers to learn about population-level brain activity and enable comparison of individual data against these norms to identify abnormalities. Currently, no standardised guide exists for transforming clinical data into a normative, regional icEEG map. Papers often cite different software and numerous articles to summarise the lengthy method, making it laborious for other researchers to understand or apply the process. Our protocol seeks to remedy this gap by providing a dataflow guide and key decision points that summarise existing methods. This protocol is used heavily in published works from our own lab (twelve peer-reviewed journal publications). Briefly, we take as input, icEEG recordings and neuroimaging data from people with epilepsy who are undergoing evaluation for resective surgery. As final outputs, we obtain a normative icEEG map, comprising signal properties localised to brain regions. Optionally, we can also process new subjects through the same pipeline and obtain their z-scores (or centiles) in each brain region, for abnormality detection and localisation. To date, a single, cohesive, dataflow pipeline for generating normative icEEG maps, along with abnormality mapping, has not been created. We envisage that this dataflow guide will not only increase understanding and application of normative mapping methods, but will also improve the consistency and quality of studies in the field.

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Multimodal Modeling of Ultradian Rhythms Using the Hankel Alternative View of Koopman (HAVOK) Analysis

Ultradian rhythms - quasi-rhythmic fluctuations in behavior and physiology with periods shorter than 24 hours - are observed across various organisms, including humans. Despite their role in key biological processes such as sleep architecture and hormone regulation, their underlying mechanisms remain poorly understood. Here, we leveraged wearable sensor technology for continuous monitoring of physiological signals in 16 healthy participants over two weeks. By systematically removing circadian and longer-scale rhythms, we isolated ultradian dynamics and modeled them using the Hankel Alternative View of Koopman (HAVOK) framework,a data-driven approach based on Takens' embedding theorem and Koopman operator theory. This allowed us to characterize ultradian rhythms as an intermittently forced linear system and distinguish between regular oscillatory behavior and more complex dynamics. Across participants, ultradian fluctuations were well-described by the HAVOK model, with intermittent forcing consistently observed. The model demonstrated strong forecasting accuracy, with root mean squared error (RMSE) of $0.0315 \pm 0.02$, $0.0306 \pm 0.02$, and $0.0218 \pm 0.02$ in the leading time-delay coordinates. Notably, a significant sex difference in model rank (z = -2.06, p = 0.0396) suggests that sex hormones may play a key role in ultradian dynamics. These findings provide evidence for intermittently forced linear systems as a useful framework for understanding ultradian rhythms and their regulation.

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Seizure duration is associated with multiple timescales in interictal iEEG band power

Background Seizure severity can change from one seizure to the next within individual people with epilepsy. It is unclear if and how seizure severity is modulated over longer timescales. Characterising seizure severity variability over time could lead to tailored treatments. In this study, we test if continuously-recorded interictal intracranial EEG (iEEG) features encapsulate signatures of such modulations. Methods We analysed 20 subjects with iEEG recordings of at least one day. We identified cycles on timescales of hours to days embedded in long-term iEEG band power and associated them with seizure severity, which we approximated using seizure duration. In order to quantify these associations, we created linear-circular statistical models of seizure duration that incorporated different band power cycles within each subject. Findings In most subjects, seizure duration was weakly to moderately correlated with individual band power cycles. Combinations of multiple band power cycles significantly explained most of the variability in seizure duration. Specifically, we found 70% of the models had a higher than 60% adjusted $R^2$ across all subjects. From these models, around 80% were deemed to be above chance-level (p-value < 0.05) based on permutation tests. Models included cycles of ultradian, circadian and slower timescales in a subject-specific manner. Interpretation These results suggest that seizure severity, as measured by seizure duration, may be modulated over timescales of minutes to days by subject-specific cycles in interictal iEEG signal properties. These cycles likely serve as markers of seizure modulating processes. Future work can investigate biological drivers of these detected fluctuations and may inform novel treatment strategies that minimise seizure severity.

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Dual mechanism of Anti-Seizure Medications in controlling seizure activity

Background: Anti-seizure medications (ASMs) can reduce seizure duration, but their precise modes of action are unclear. Specifically, it is unknown whether ASMs shorten seizures by simply compressing existing seizure activity into a shorter time frame or by selectively suppressing certain seizure activity patterns. Methods: We analysed intracranial EEG (iEEG) recordings of 457 seizures from 28 people with epilepsy undergoing ASM tapering. Beyond measuring seizure occurrence and duration, we categorized distinct seizure activity patterns (states) based on spatial and frequency power characteristics and related these to different ASM levels. Results: We found that reducing ASM levels led to increased seizure frequency (r = 0.87, p < 0.001) and longer seizure duration ($β$ = -0.033, p < 0.001), consistent with prior research. Further analysis revealed two distinct mechanisms in which seizures became prolonged: Emergence of new seizure patterns - In approx. 40% of patients, ASM tapering unmasked additional seizure activity states, and seizures containing these 'taper-emergent states' were substantially longer (r = 0.49, p < 0.001). Prolongation of existing seizure patterns - Even in seizures without taper-emergent states, lower ASM levels still resulted in approx. 12-224% longer durations depending on the ASM dosage and tapering ($β$ = -0.049, p < 0.001). Conclusion: ASMs influence seizures through two mechanisms: they (i) suppress specific seizure activity patterns (states) in an all-or-nothing fashion and (ii) curtail the duration of other seizure patterns. These findings highlight the complex role of ASMs in seizure modulation and could inform personalized dosing strategies for epilepsy management. These findings may also have implications in understanding the effects of ASMs on cognition and mood.

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More variable circadian rhythms in epilepsy captured by long-term heart rate recordings from wearable sensors

Objective: The circadian rhythm synchronizes physiological and behavioural patterns with the 24-hour light-dark cycle. Disruption to the circadian rhythm is linked to various health conditions, though optimal methods to describe these disruptions remain unclear. An emerging approach is to examine the intra-individual variability in measurable properties of the circadian rhythm over extended periods. Epileptic seizures are modulated by circadian rhythms, but the relevance of circadian rhythm disruption in epilepsy remains unexplored. Our study investigates intra-individual circadian variability in epilepsy and its relationship with seizures. Methods: We retrospectively analyzed over 70,000 hours of wearable smartwatch data (Fitbit) from 143 people with epilepsy (PWE) and 31 healthy controls. Circadian oscillations in heart rate time series were extracted, daily estimates of circadian period, acrophase, and amplitude properties were produced, and estimates of the intra-individual variability of these properties over an entire recording were calculated. Results: PWE exhibited greater intra-individual variability in period (76 min vs. 57 min, d=0.66, p<0.001) and acrophase (64 min vs. 48 min, d=0.49, p=0.004) compared to controls, but not in amplitude (2 bpm, d=-0.15, p=0.49). Variability in circadian properties showed no correlation with seizure frequency, nor any differences between weeks with and without seizures. Significance: For the first time, we show that heart rate circadian rhythms are more variable in PWE, detectable via consumer wearable devices. However, no association with seizure frequency or occurrence was found, suggesting that this variability might be underpinned by the epilepsy aetiology rather than being a seizure-driven effect.

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Combined impact of grey and superficial white matter abnormalities: implications for epilepsy surgery

Drug-resistant focal epilepsy is associated with abnormalities in the brain in both grey matter (GM) and superficial white matter (SWM). However, it is unknown if both types of abnormalities are important in supporting seizures. Here, we test if surgical removal of GM and/or SWM abnormalities relates to post-surgical seizure outcome in people with temporal lobe epilepsy (TLE). We analyzed structural imaging data from 143 TLE patients (pre-op dMRI and pre-op T1-weighted MRI) and 97 healthy controls. We calculated GM volume abnormalities and SWM mean diffusivity abnormalities and evaluated if their surgical removal distinguished seizure outcome groups post-surgically. At a group level, GM and SWM abnormalities were most common in the ipsilateral temporal lobe and hippocampus in people with TLE. Analyzing both modalities together, compared to in isolation, improved surgical outcome discrimination (GM AUC = 0.68, p < 0.01, WM AUC = 0.65, p < 0.01; Union AUC = 0.72, p < 0.01, Concordance AUC = 0.64, p = 0.04). Additionally, 100% of people who had all concordant abnormal regions resected had ILAE$_{1,2}$ outcomes. These findings suggest that regions identified as abnormal from both diffusion-weighted and T1-weighted MRIs are involved in the epileptogenic network and that resection of both types of abnormalities may enhance the chances of living without disabling seizures.

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Automated generation of epilepsy surgery resection masks; The RAMPS pipeline

MRI-based delineation of brain tissue removed by epilepsy surgery can be challenging due to post-operative brain shift. In consequence, most studies use manual approaches which are prohibitively time-consuming for large sample sizes, require expertise, and can be prone to errors. We propose RAMPS (Resections And Masks in Preoperative Space), an automated pipeline to generate a 3D resection mask of pre-operative tissue. Our pipeline leverages existing software including FreeSurfer, SynthStrip, Sythnseg and ANTS to generate a mask in the same space as the patient's pre-operative T1 weighted MRI. We compare our automated masks against manually drawn masks and two other existing pipelines (Epic-CHOP and ResectVol). Comparing to manual masks (N=87), RAMPS achieved a median(IQR) dice similarity of 0.86(0.078) in temporal lobe resections, and 0.72(0.32) in extratemporal resections. In comparison to other pipelines, RAMPS had higher dice similarities (N=62) (RAMPS:0.86, Epic-CHOP: 0.72, ResectVol: 0.72). We release a user-friendly, easy to use pipeline, RAMPS, open source for accurate delineation of resected tissue.

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Comparing Methodological Variations in Seizure Onset Localisation Algorithms using intracranial EEG

During clinical treatment for epilepsy, the area of the brain thought to be responsible for pathological activity is identified. This identification is typically performed through visual assessment of EEG recordings; however, this is time consuming and prone to subjective inconsistency. Automated onset localisation algorithms provide objective identification of the onset location by highlighting changes in signal features associated with seizure onset. In this work we investigate how methodological differences in such algorithms can result in different onset locations being identified. We analysed ictal intracranial EEG (icEEG) recordings in 16 subjects (100 seizures) with drug-resistant epilepsy from the SWEZ-ETHZ public database. We identified a series of key methodological differences that must be considered when designing or selecting an onset localisation algorithm. These differences were demonstrated using three distinct algorithms that capture different, but complementary, seizure onset features: Imprint, Epileptogenicity Index, and Low Entropy Map. We assessed methodological differences (or Decision Points), and their impact on the identified onset locations. Our independent application of all three algorithms to the same ictal icEEG dataset revealed low agreement between them: 27-60% of onset channels showed minimal or no overlap. Therefore, we investigated the effect of three key differences: (i) how to define a baseline, (ii) whether low-frequency components are considered, and finally (iii) whether electrodecrement is considered. Changes at each Decision Point were found to substantially influence resultant onset channels (r>0.3). Our results demonstrate how seemingly small methodological changes can result in large differences in onset locations. We propose that key Decision Points must be considered when using or designing an onset localisation algorithm.

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Anti-seizure medication tapering correlates with daytime delta band power reduction in the cortex

Anti-seizure medications (ASMs) are the primary treatment for epilepsy, yet medication tapering effects have not been investigated in a dose, region, and time-dependent manner, despite their potential impact on research and clinical practice. We examined over 3000 hours of intracranial EEG recordings in 32 subjects during long-term monitoring, of which 22 underwent concurrent ASM tapering. We estimated ASM plasma levels based on known pharmaco-kinetics of all the major ASM types. We found an overall decrease in the power of delta band activity around the period of maximum medication withdrawal in most (80%) subjects, independent of their epilepsy type or medication combination. The degree of withdrawal correlated positively with the magnitude of delta power decrease. This dose-dependent effect was evident across all recorded cortical regions during daytime; but not in sub-cortical regions, or during night time. We found no evidence of a differential effect in seizure onset, spiking, or pathological brain regions. The finding of decreased delta band power during ASM tapering agrees with previous literature. Our observed dose-dependent effect indicates that monitoring ASM levels in cortical regions may be feasible for applications such as medication reminder systems, or closed-loop ASM delivery systems. ASMs are also used in other neurological and psychiatric conditions, making our findings relevant to a general neuroscience and neurology audience.

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Multiscale cortical morphometry reveals pronounced regional and scale-dependent variations across the lifespan

Motivation: Characterising the changes in cortical morphology across the lifespan is fundamental for a range of research and clinical applications. Most studies to date have found a monotonic decrease in commonly used morphometrics, such as cortical thickness and volume, across the entire brain with increasing age. Any regional variations reported are subtle changes in the rate of decrease. However, these descriptions of morphological changes have been limited to a single length scale. Here, we delineate the morphological changes associated with the healthy lifespan in multiscale morphometrics. Methods: We applied multiscale morphometric analysis to structural MRI from subjects aged 6-88 years from NKI (n=833) and CamCAN (n=641). These multiscale morphometrics were obtained at both the cortical hemisphere and lobe level. Results: On the level of whole cortical hemispheres, lifespan trajectories show diverging and even opposing trends at different spatial scales, in contrast to the monotonic decreases of volume and thickness described so far. Importantly, larger scales displayed most dramatic changes across the lifespan (up to 60%). More pronounced lobal differences in lifespan trajectories also became apparent in scales over 0.7mm. In a proof-of-principle application in brain age prediction, we also demonstrate added information contributed by multiscale morphometrics. Conclusion: Our study provides a comprehensive multiscale description of lifespan effects on cortical morphology in an age range from 6-88~years. In future, this can form the foundations for a normative model to compare individuals or cohorts, hence identifying multiscale morphological abnormalities. Our results reveal the complementary information contained in different spatial scales, suggesting that morphometrics should not be considered on a single scale, but as functions of length scale.

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Multi-centre normative brain mapping of intracranial EEG lifespan patterns in the human brain

Background: Understanding healthy human brain function is crucial to identify and map pathological tissue within it. Whilst previous studies have mapped intracranial EEG (icEEG) from non-epileptogenic brain regions, these maps do not consider the effects of age and sex. Further, most existing work on icEEG has often suffered from a small sample size due to the modality's invasive nature. Here, we substantially increase the subject sample size compared to existing literature, to create a multi-centre, normative map of brain activity which additionally considers the effects of age, sex and recording hospital. Methods: Using interictal icEEG recordings from n = 502 subjects originating from 15 centres, we constructed a normative map of non-pathological brain activity by regressing age and sex on relative band power in five frequency bands, whilst accounting for the hospital effect. Results: Recording hospital significantly impacted normative icEEG maps in all frequency bands, and age was a more influential predictor of band power than sex. The age effect varied by frequency band, but no spatial patterns were observed at the region-specific level. Certainty about regression coefficients was also frequency band specific and moderately impacted by sample size. Conclusion: The concept of a normative map is well-established in neuroscience research and particularly relevant to the icEEG modality, which does not allow healthy control baselines. Our key results regarding the hospital site and age effect guide future work utilising normative maps in icEEG.

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Status epilepticus and thinning of the entorhinal cortex

Status epilepticus (SE) carries risks of morbidity and mortality. Experimental studies have implicated the entorhinal cortex in prolonged seizures; however, studies in large human cohorts are limited. We hypothesised that individuals with temporal lobe epilepsy (TLE) and a history of SE would have more severe entorhinal atrophy compared to others with TLE and no history of SE. 357 individuals with drug resistant temporal lobe epilepsy (TLE) and 100 healthy controls were scanned on a 3T MRI. For all subjects the cortex was segmented, parcellated, and the thickness calculated from the T1-weighted anatomical scan. Subcortical volumes were derived similarly. Cohen's d and Wilcoxon rank-sum tests respectively were used to capture effect sizes and significance. Individuals with TLE and SE had reduced entorhinal thickness compared to those with TLE and no history of SE. The entorhinal cortex was more atrophic ipsilaterally (d=0.51, p<0.001) than contralaterally (d=0.37, p=0.01). Reductions in ipsilateral entorhinal thickness were present in both left TLE (n=22:176, d=0.78, p<0.001), and right TLE (n=19:140, d=0.31, p=0.04), albeit with a smaller effect size in right TLE. Several other regions exhibited atrophy in individuals with TLE, but these did not relate to a history of SE. These findings suggest potential involvement or susceptibility of the entorhinal cortex in prolonged seizures.

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Neuro-evolutionary evidence for a universal fractal primate brain shape

The cerebral cortex displays a bewildering diversity of shapes and sizes across and within species. Despite this diversity, we present a universal multi-scale description of primate cortices. We show that all cortical shapes can be described as a set of nested folds of different sizes. As neighbouring folds are gradually merged, the cortices of 11 primate species follow a common scale-free morphometric trajectory, that also overlaps with over 70 other mammalian species. Our results indicate that all cerebral cortices are approximations of the same archetypal fractal shape with a fractal dimension of $d_f=2.5$. Importantly, this new understanding enables a more precise quantification of brain morphology as a function of scale. To demonstrate the importance of this new understanding, we show a scale-dependent effect of ageing on brain morphology. We observe a more than four-fold increase in effect size (from 2 standard deviations to 8 standard deviations) at a spatial scale of approximately 2 mm compared to standard morphological analyses. Our new understanding may therefore generate superior biomarkers for a range of conditions in the future.

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The Imaging Database for Epilepsy And Surgery (IDEAS)

Magnetic resonance imaging (MRI) is a crucial tool to identify brain abnormalities in a wide range of neurological disorders. In focal epilepsy MRI is used to identify structural cerebral abnormalities. For covert lesions, machine learning and artificial intelligence algorithms may improve lesion detection if abnormalities are not evident on visual inspection. The success of this approach depends on the volume and quality of training data. Herein, we release an open-source dataset of preprocessed MRI scans from 442 individuals with drug-refractory focal epilepsy who had neurosurgical resections, and detailed demographic information. The MRI scan data includes the preoperative 3D T1 and where available 3D FLAIR, as well as a manually inspected complete surface reconstruction and volumetric parcellations. Demographic information includes age, sex, age of onset of epilepsy, location of surgery, histopathology of resected specimen, occurrence and frequency of focal seizures with and without impairment of awareness, focal to bilateral tonic-clonic seizures, number of anti-seizure medications (ASMs) at time of surgery, and a total of 1764 patient years of post-surgical follow up. Crucially, we also include resection masks delineated from post-surgical imaging. To demonstrate the veracity of our data, we successfully replicated previous studies showing long-term outcomes of seizure freedom in the range of around 50%. Our imaging data replicates findings of group level atrophy in patients compared to controls. Resection locations in the cohort were predominantly in the temporal and frontal lobes. We envisage our dataset, shared openly with the community, will catalyse the development and application of computational methods in clinical neurology.

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