arXiv subjects

Billy Smith

Publications and source records attributed to Billy Smith.

3 recordsLinked to original sources

arXiv2025

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 ($\beta$ = -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 ($\beta$ = -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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arXiv2024

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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arXiv2024

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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