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Philippa J. Karoly

Publications and source records attributed to Philippa J. Karoly.

5 recordsLinked to original sources

Temporally constraining source imaging estimates in an underdetermined neural system with eigenmodes of cortical geometry

Geometric eigenmodes provide a compact and biologically grounded representation of large-scale neural activity. Previous work demonstrated that they can mitigate the underdetermined nature of electroencephalographic (EEG) and magnetoencephalographic (MEG) source localisation, an ill-posed inverse problem in which neural activity is reconstructed from non-invasive recordings. Beyond their spatial structure, neural field theory predicts the temporal evolution of eigenmodes through analytically derived transfer functions. Motivated by this framework, the present work investigates whether these transfer functions can be used to introduce temporal constraints into EEG source imaging. The approach is evaluated using simulated seizure dynamics generated by coupled Epileptor neural mass models. Transfer functions derived directly from neural field theory were found to be generally ineffective as temporal constraints for source localisation, primarily because they neglect cross-eigenmode coupling. Incorporating empirically estimated coupling terms substantially improves localisation performance, particularly in noisy conditions. Although estimating these eigenmode coupling interactions from experimental data remains challenging, the findings motivate dynamical source imaging approaches that combine spatial eigenmode structure with empirically informed cross-modal dynamics.

q-bio.NC

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.

q-bio.QM

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.

q-bio.NC

Chronic iEEG recordings and interictal spike rate reveal multiscale temporal modulations in seizure states

Background and Objectives: Many biological processes are modulated by rhythms on circadian and multidien timescales. In focal epilepsy, various seizure features, such as spread and duration, can change from one seizure to the next within the same patient. However, the specific timescales of this variability, as well as the specific seizure characteristics that change over time, are unclear. Methods: Here, in a cross-sectional observational study, we analysed within-patient seizure variability in 10 patients with chronic intracranial EEG recordings (185-767 days of recording time, 57-452 analysed seizures/patient). We characterised the seizure evolutions as sequences of a finite number of patient-specific functional seizure network states (SNSs). We then compared SNS occurrence and duration to (1) time since implantation and (2) patient-specific circadian and multidien cycles in interictal spike rate. Results: In most patients, the occurrence or duration of at least one SNS was associated with the time since implantation. Some patients had one or more SNSs that were associated with phases of circadian and/or multidien spike rate cycles. A given SNS's occurrence and duration were usually not associated with the same timescale. Discussion: Our results suggest that different time-varying factors modulate within-patient seizure evolutions over multiple timescales, with separate processes modulating a SNS's occurrence and duration. These findings imply that the development of time-adaptive treatments in epilepsy must account for several separate properties of epileptic seizures, and similar principles likely apply to other neurological conditions.

q-bio.NC

Seizure pathways and seizure durations can vary independently within individual patients with focal epilepsy

A seizure's electrographic dynamics are characterised by its spatiotemporal evolution, also termed dynamical "pathway" and the time it takes to complete that pathway, which results in the seizure's duration. Both seizure pathways and durations can vary within the same patient, producing seizures with different dynamics, severity, and clinical implications. However, it is unclear whether seizures following the same pathway will have the same duration or if these features can vary independently. We compared within-subject variability in these seizure features using 1) epilepsy monitoring unit intracranial EEG (iEEG) recordings of 31 patients (mean 6.7 days, 16.5 seizures/subject), 2) NeuroVista chronic iEEG recordings of 10 patients (mean 521.2 days, 252.6 seizures/subject), and 3) chronic iEEG recordings of 3 dogs with focal-onset seizures (mean 324.4 days, 62.3 seizures/subject). While the strength of the relationship between seizure pathways and durations was highly subject-specific, in most subjects, changes in seizure pathways were only weakly to moderately associated with differences in seizure durations. The relationship between seizure pathways and durations was weakened by seizures that 1) had a common pathway, but different durations ("elastic pathways"), or 2) had similar durations, but followed different pathways ("duplicate durations"). Even in subjects with distinct populations of short and long seizures, seizure durations were not a reliable indicator of different seizure pathways. These findings suggest that seizure pathways and durations are modulated by different processes. Uncovering such modulators may reveal novel therapeutic targets for reducing seizure duration and severity.

q-bio.NC