Increased gamma and decreased fast ripple connections of epileptic tissue: A high‐frequency directed network approach

Zweiphenning, Willemiek; Keijzer, Hanneke M.; Diessen, Eric van; Klooster, Maryse A. van ‘t; Klink, Nicole E.C. van; Leijten, Frans S.S.; Rijen, Peter C. van; Putten, Michel J.A.M. van; Braun, Kees P.J.; Zijlmans, Maeike

doi:10.1111/epi.16296

Cited by 30 publications

(35 citation statements)

References 48 publications

(162 reference statements)

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“…This suggests that, in addition to low PSD, increased gamma may also be used as a marker for the severity of epilepsy. Corroborating this hypothesis, gamma band activity in epilepsy patients was shown to be higher in epileptic foci (Ren et al, 2015), and surgical removal of areas with high gamma resulted in a better outcome (Zweiphenning et al, 2019).…”

Section: Reduced Eeg Power At the Worsening Stage Of Dravetmentioning

confidence: 87%

Early EEG and behavioral alterations in Dravet mice

Fadila

Quinn

Maia

et al. 2020

Preprint

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Dravet Syndrome (Dravet) is a severe childhood epileptic encephalopathy. The disease begins around the age of six months, with a febrile stage, characterized by febrile seizures with otherwise normal development. By the end of the first year of life, the disease progresses to the worsening stage, featuring recurrent intractable seizures and the appearance of additional comorbidities, including global developmental delay, cognitive deficits, hyperactivity and motor problems. Later, in early school years, Dravet reaches the stabilization stage, in which seizure burden decreases, while Dravet-associated comorbidities persist. Dravet syndrome mouse models (DS) faithfully recapitulate the three stages of the human syndrome. Here, we performed power spectral analyses of background EEG activity in DS and their wild-type (WT) littermates, demonstrating disease stagerelated alterations. Specifically, while the febrile stage activity resembled that of WT mice, we observed a marked reduction in total power during the worsening stage and a smaller reduction during the stabilization stage. Moreover, low EEG power at the worsening stage correlated with increased risk for premature death, suggesting that such measurements can potentially be used as a marker for Dravet severity. With normal development at the febrile stage and the presentation of developmental delay at the worsening stage, the contribution of recurrent seizures to the emergence of Dravet-associated comorbidities is still debated.Thus, we further characterized the behavior of WT and DS mice during the different stages of Dravet. At the febrile stage, despite their normal background EEG patterns, DS mice already demonstrated motor impairment and hyperactivity in the open field, that persisted to the worsening and stabilization stages. Conversely, clear evidence for deficits in working memory emerged later in life, during the worsening stage. These results indicate that despite the mild epilepsy at the febrile stage, DS development is already altered, suggesting that the pathophysiological mechanisms governing the appearance of some Dravet behavioral comorbidities may be independent of the epileptic phenotype. Highlights • Reduction in background EEG power in Dravet• Low EEG power correlates with the risk of premature death• Motor deficits and hyperactivity are evident as early as the febrile stage • Cognitive deficits and detection of increased anxiety begin at the worsening stage 10 min, and were selected from throughout the entire recording. Spikes were detected using LabChart 8 software (ADInstruments, Sydney, Australia). The threshold was set to 7 standard divisions, and their maximal allowed duration was set to 250 ms. Early motor activityWT and DS mice were tested from P8 to P11. Mice were individually placed in the middle of a 13 cm wide circle and the latency to cross the drawn borders of the circle was measured. The test was repeated three times and averaged. If the mouse was unable to cross the border of the circle within 1 min, the test was terminated. ...

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Section: Reduced Eeg Power At the Worsening Stage Of Dravetmentioning

confidence: 87%

Early EEG and behavioral alterations in Dravet mice

Fadila

Quinn

Maia

et al. 2020

Preprint

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“…Furthermore, the perturbational approach may benefit from the use of coordinated stimulation in different regions, since changes heralding the approach of ictal activity were visible not only in the ictogenic population activity, but also in the coupled neuronal populations with fixed parameters (as in the case of model setting II-A). This is especially relevant, considering that refractory epilepsy is increasingly being considered as a network disease [84]. The combination of stimulation of the ictal onset zone and remote structures has been shown previously to further increase DBS efficacy in epilepsy patients [85].…”

Section: Discussionmentioning

confidence: 99%

Active probing to highlight approaching transitions to ictal states in coupled neural mass models

Carvalho

Moraes

Cash

et al. 2020

Preprint

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The extraction of electrophysiological features that reliably forecast the occurrence of seizures is one of the most challenging goals in epilepsy research. Among possible approaches to tackle this problem is the use of active probing paradigms in which responses to stimuli are used to detect underlying system changes leading up to seizures. This work evaluates the theoretical and mechanistic underpinnings of this strategy using a well-studied seizure-generating neural mass model with two coupled populations. Different simulations are done by shifting parameters (excitability, slow inhibition, and coupling gains) towards ictal states while low-frequency probing stimuli are applied to either one or both populations. The correlation between the extracted features and the shifted parameter indicates if the impending transition to the ictal state may be identified in advance. Results show that not only can the response to the probing stimuli forecast seizures but this is true regardless of the altered ictogenic parameter. That is, similar feature changes are highlighted by probing stimuli responses in advance of the seizure including: increased response variance and lag-1 autocorrelation, decreased skewness, and increased mutual information between the outputs of both model subsets. These changes were restricted to the stimulated population, showing a local effect of this perturbational approach. The transition latencies from normal activity to sustained discharges of spikes were not affected, suggesting that stimuli had no pro-ictal effects. However, stimuli were found to elicit interictal-like spikes just before the transition to the ictal state. Furthermore, the observed feature changes highlighted by probing the neuronal populations may reflect the phenomenon of critical slowing down, where increased recovery times from perturbations may signal the loss of a systems’ resilience and are common hallmarks of an impending critical transition. These results provide more evidence that active probing approaches highlight information about underlying system changes involved in ictogenesis and may be able to play a role in assisting seizure forecasting methods which can be incorporated into early-warning systems that ultimately enable closing the loop for targeted seizure-controlling interventions.Author summaryEpilepsy is characterized by spontaneous and recurrent seizures. Developing a method to forecast the occurrence of these events would ease part of the burden to patients by providing warning systems and identifying critical periods for closed-loop seizure suppressing methods. However, this task is far from trivial and doing this in a clinical setting has been a challenge that is not yet solved. A possible way to achieve this is by using active probing paradigms, in which stimuli are used to highlight otherwise hidden changes in brain dynamics that may lead to seizures. In this work, this approach is tested in a computational model with two coupled neuronal populations. Active probing responses highlighted underlying model parameter changes that led neuronal activity closer to seizures, something that was not detected with the passive observation in most evaluated model settings. Observed feature changes revealed higher excitability, longer recovery times from stimuli, and increased synchrony between populations as the threshold to seizure-like activity approached. This indicates that low frequency stimuli may be used to reveal early-warning signs and assist in seizure forecasting methods.

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“…We chose our biomarkers with two criteria in mind: 1) to be exhaustive regarding the different types of measures used (i.e. univariate, bivariate and multivariate); 2) biomarkers should have been reported to show an overall significant effect in discriminating between healthy and pathological tissue using inter-ictal intracranial recordings [23][24][25][27][28][29][31][32][33][34][35]60 .…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that using certain biomarkers the epileptogenic tissue can be distinguished from the healthy tissue based on inter-ictal intracranial recordings [22][23][24][25][26][27][28][29] , but only statistically on the aggregate group level. A biomarker set is needed that discriminates well between tissue that needs to be surgically removed and tissue that should not at the patient level, which can thus be applied for clinical care.…”

Section: Introductionmentioning

confidence: 99%

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To resect or not to resect? Unbiased performances of single and combined biomarkers in intra-operative corticography for tailoring during epilepsy surgery

Demuru

Kalitzin

Zweiphenning

et al. 2019

Preprint

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Objective:Signal analysis biomarkers, in an intra-operative setting, may be complementary tools to guide and tailor the resection in drug-resistant epilepsy patients. Unbiased assessment of biomarker performances are needed to evaluate their clinical usefulness and translation. We defined a realistic ground-truth scenario and compared the effectiveness of different biomarkers alone and combined to localize epileptogenic tissue. Methods:We investigated the performances of univariate, bivariate and multivariate signal biomarkers applied to 1 minute inter-ictal intra-operative electrocorticography to discriminate between electrodes covering normal or pathologic activity in 47 drug-resistant people with epilepsy (temporal and extra-temporal) who had been seizure-free one year after the operation. Results:The best result using a single biomarker was obtained using the phase-amplitude coupling measure for which the epileptogenic tissue was localized in 16 out of 47 patients. Combining the whole set of biomarkers provided an improvement of the performances: 20 out of 47 patients. Repeating the analysis only on the temporal-lobe resections we reached a sensitivity of 93% (28 out of 30) combining all the biomarkers. Conclusion:We suggest that the assessment of biomarker performances on a ground-truth scenario is required to have a proper estimate on how biomarkers translate into clinical use. Phase-amplitude coupling seems the best performing single biomarker and combining biomarkers improves localization of epileptogenic tissue. However, sensitivity achieved is not adequate for the usage as a tool in the operation theater, but it can improve the understanding of pathophysiological process.

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Increased gamma and decreased fast ripple connections of epileptic tissue: A high‐frequency directed network approach

Cited by 30 publications

References 48 publications

Early EEG and behavioral alterations in Dravet mice

Early EEG and behavioral alterations in Dravet mice

Active probing to highlight approaching transitions to ictal states in coupled neural mass models

To resect or not to resect? Unbiased performances of single and combined biomarkers in intra-operative corticography for tailoring during epilepsy surgery

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