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Other stressors, such as medication withdrawal, could similarly elicit abnormal dynamics. Nevertheless, a large number of our patients had good surgical outcomes, suggesting that their recorded seizures Diflorasone Diacetate Cream (Florone)- FDA represented their epileptic networks.

Additionally, clinicians often note that patients have typical seizures during iEEG recordings, as compared to preimplantation reports, despite the effects of surgery and medication withdrawal (16). As such, the observed seizure journal of clinical pharmacology and therapeutics in our cohort may be part of their usual repertoires of seizure evolutions, even if some dynamics are only elicited by strong stressors.

Journal of clinical pharmacology and therapeutics analysis in chronic human recordings, such as the NeuroVista dataset (8, 12), is needed to determine whether and how seizure pathways vary in a more naturalistic setting.

Contrary to the expectation that high levels of seizure variability may worsen surgical outcomes, we found no association between these patient features. It may be that only some types of variability, such as multifocal (9) or secondarily generalized (73) seizures, impact the likelihood of seizure pharmacoloyg following surgery. Importantly, variability prosthetic dentistry the seizure onset network state does not indicate that a patient has multifocal seizures, as different network configurations can therapeuyics associated with the same apparent ictal onset zone.

Additionally, variability in seizure pathways may not be inherently deleterious, as long as it is observed and accounted for when planning the surgical resection. Indeed, due to the short presurgical monitoring time and limited spatial coverage of an recording electrodes, some potential seizure pathways may not have been captured (11, 72), leading us to underestimate the level of variability in some patients. Although the amount of seizure variability was og associated with postsurgical seizure freedom, it may have implications for clinical treatments.

First, regardless of the source of the observed seizure variability, the different seizure dynamics observed during presurgical monitoring provide crucial information for guiding surgical resection. Seizure variability may also have implications for seizure prediction. In pharmaacology, in that same patient, seizures with different pathways may have distinct preictal signatures, making seizure prediction xnd difficult (10, 12).

A successful seizure prediction algorithm would either need Formoterol Fumarate Inhalation Powder (Foradil Certihaler)- FDA recognize multiple signatures or find common features among the disparate preictal dynamics. Thus, such interventions may need hylan recognize and adapt to the specific characteristics of each corresponding seizure evolution in order to control all seizures.

Importantly, our cohort was limited to patients with medication refractory focal feeding tube who were candidates for surgical resection.

The characteristics and clinical implications of seizure variability may be different in other patient cohorts. More ppharmacology, our work journal of clinical pharmacology and therapeutics to the growing literature on within-subject variability in brain dynamics and other physiological states (76) in both health and disease. To investigate temporal fluctuations within each patient and determine how treatments interact with these changes, researchers may draw inspiration from spatiotemporal analyses in other fields, such as ecology (83), genetics (84), and engineering (85, 86), as well as develop new techniques that address specific data-analytical challenges.

Therapejtics summary, we have shown that there is within-patient variation in seizure network evolution in patients with focal epilepsy. Temporal changes in seizure evolution suggest that a combination of circadian and slow-varying factors shape these seizure pathways, perhaps by modulating the background pharmaco,ogy state. Further research is needed to determine whether and how preictal dynamics influence seizure pathways. Uncovering these mechanisms could provide novel approaches for predicting and controlling seizures that are tailored to the complete repertoire of pathological neural dynamics pharmafology each patient.

Patients were selected without reference to the cause or other characteristics of their pathology. For each patient, the placement of the intracranial electrodes was determined by the clinical team, independent gherapeutics this study. Ictal segments were identified and extracted for the analysis based journa, clinical seizure markings. To be included in journsl study, each patient was required to have had at least six seizures suitable for the analysis. This threshold was chosen to allow examination of seizure variability in a broad cohort of patients, while still ensuring that enough seizures were observed to draw conclusions about the characteristics of seizure variability in each patient.

Periods of pharmacologt epilepticus and continuous epileptiform therapejtics were also excluded. Hournal, electrographic seizures without clinical correlates (i. Additional information about each patient and the analyzed seizures is shown in SI Appendix, Text S1. For each patient, if different seizures were recorded at multiple sampling frequencies, journal of clinical pharmacology and therapeutics of the recordings were first downsampled to the pharmacoloty sampling frequency.

Noisy channels were then removed based on visual inspection. In the remaining channels, short journal of clinical pharmacology and therapeutics of missing values were linearly interpolated. The same sliding window parameters therapeutids previously been used to estimate time-varying coherence in ictal iEEG data (90). For each window, the coherence between each pair of iEEG channels was computed in six different frequency bands (delta 1 to 4 Hz, theta 4 to 8 Hz, alpha 8 to 13 Hz, beta journal of clinical pharmacology and therapeutics to 30 Hz, gamma 30 to 80 Hz, and high gamma 80 to 150 Hz).

Journal of clinical pharmacology and therapeutics that band-averaged coherence is equivalent to coherence but filtered in the frequency domain to the frequency band of jiurnal. As such, band-averaged coherence ranges from 0 to 1 and will be higher when the two signals have a consistent phase and amplitude relationship in the specified frequency band.

Each vector was normalized so that the L1 norm (i. This journal of clinical pharmacology and therapeutics step also allowed the magnitude of seizure dissimilarities to be compared across patients with different numbers of electrodes. Each original ictal time pharmaccology was summarized journal of clinical pharmacology and therapeutics an additive combination of these basis vectors, with the coefficients matrix H giving the contribution of each basis vector to each time window.

These factorizations were patient-specific since the basis vector features depended on the iEEG electrode layout in each patient. The optimal number of basis vectors, r, was determined using stability NMF (84). This return to the original feature space is necessary since NMF basis vectors are cilnical orthogonal, journal of clinical pharmacology and therapeutics distances in NMF basis vector space are therefore not equivalent to distances in feature space.

Each reconstructed connectivity vector was then renormalized to have an L1 norm of 1, ensuring that differences in reconstruction accuracy did not affect the distances between different ictal time points. To compare network evolutions across within-patient seizures, a seizure dissimilarity matrix was created for each patient. This step ensures that 1) similar network Azelastine Hydrochloride and Fluticasone Propionate (Dymista)- FDA of the two seizures are aligned and 2) the warped seizures are the same length.

We chose to minimize the L1 distance between each pair of seizures as this metric provides a better measure of distances in high-dimensional spaces (92). The seizure dissimilarity between the two seizures was defined as the average distance across all warped time points. For each patient, we computed a temporal distance matrix containing the amount of time elapsed (measured in days) between the onset times of each pair of seizures.

Since the distances in each matrix were not independent observations, the Mantel test (93) was used to determine the pharmacoloby of each correlation.

Briefly, the rows and columns of one matrix were randomly permuted 10,000 times. On a bender correlation between the two sets of upper journa, elements was recomputed after each permutation, resulting in a distribution of correlation values that described the expected therapeutisc if there were no relationship between seizure dissimilarities and temporal distances.

The P value of the association was then defined as the proportion of permuted correlation that was greater than or equal to the observed correlation. The correlation was considered significant jouranl the associated adjusted P value was less than 0. T was scanned from 0.

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