Artificial neural network trained on smartphone behavior can trace epileptiform activity in epilepsy

Clinical Neurophysiology: EEG–Video Monitoring

This case study examined the association between epileptic activity such as epileptiform discharges and autistic symptoms; and to examine the effect of mTOR inhibitor everolimus on seizures and epileptiform discharges in three cases with TSC and autistic symptoms. The everolimus treatment improved autistic symptoms in all four cases, however, epileptiform discharges did not disappear in all four cases with everolimus treatment. Thus, epileptiform activity and autistic symptoms may be two end-results of separate brain dysfunction. The evrolimus treatment disappeared a seizure in only one case, suggesting partial overlap between mTOR hyperactivity and a seizure in small subset of cases with TSC. This study for firstly revealed that the everolimus treatment was inefficient for epileptiform discharges. Antiepileptic therapy at early stage of brain development might be effective for epileptic activity.

Purpose:To study the epileptiform discharges (EDs) in the electroencephalogram (EEG) of 6-8-year-old children of women with epilepsy (WWE).Materials and Methods:All children born to women with epilepsy and prospectively followed up through the Kerala Registry of Epilepsy and Pregnancy (KREP), aged 6–8 years, were invited (n = 532). Out of the 254 children who responded, clinical evaluations and a 30-min digital 18 channel EEG were completed in 185 children.Results:Of the 185 children examined, 37 (20%) children (19 males, 18 females) had ED in their EEG. The EDs were generalized in 7 children, and focal in 30 children. The EDs were present in the sleep record only of 16 (43%) children and in the awake record only of 6 (16%) children. Out of the 94 children for whom seizure history was available, 7 children (7.4%) had seizures (neonatal seizures: 4, febrile seizure: 1, and single nonfebrile seizure: 2) and none had history of epilepsy or recurrent nonfebrile seizures. The odds ratio (OR) for occurrence of ED in the EEG was significantly higher for children of WWE [OR = 3.5, 95% confidence interval (CI) 2.3-6.0] when compared to the published data for age-matched children of mothers without epilepsy. There was no association between the occurrence of ED and the children's maternal characteristics [epilepsy syndrome, seizures during pregnancy, maternal intelligence quotient (IQ)] or the children's characteristics [antenatal exposure to specific antiepileptic drugs (AEDs), birth weight, malformations, IQ].Conclusion:Children of WWE have a higher risk of epileptiform activity in their EEG when compared to healthy children in the community though none had recurrent seizures.

The role of gamma-aminobutyric acid B (GABA(B)) receptors in the generation and maintenance of bicuculline-induced epileptiform activity in rat neocortical slices was studied using electrophysiological methods. A block of GABA(B) receptors in the presence of functional GABA(A) receptor-mediated inhibition was not sufficient to induce epileptiform activity. In the presence of the GABA(A) receptor antagonist bicuculline (10 microM) and at suprathreshold stimulation, the GABA(B) receptor antagonist CGP 35348 (10-300 microM) significantly potentiated epileptiform activity. With stimulation at threshold intensity, low concentrations of CGP 35348 (10-30 microM) potentiated bicuculline-induced activity, whereas higher concentrations (100-300 microM) invariably led to a reversible suppression of stimulus-evoked epileptiform discharges. CGP 35348 also enhanced picrotoxin-induced epileptiform activity, but at higher concentrations it was considerably less effective in suppressing such epileptiform discharges. The GABA uptake inhibitor nipecotic acid partially mimicked the actions of CGP 35348: with stimulation at threshold intensity, it reversibly suppressed bicuculline-induced epileptiform field potentials, but it did not influence epileptiform activity induced by picrotoxin. We conclude that a postsynaptic blockade of GABA(B) receptors induces an amplification of epileptiform activity in neocortical slices disinhibited by GABA(A) receptor antagonists. An additional blockade of presynaptic GABA(B) receptors, especially under conditions of weak stimulation of the neurons, reduces the inhibitory auto-feedback control of GABA release, leading to a displacement of competitive antagonists from the postsynaptic GABA(A) receptor and hence, to a suppression of epileptiform activity induced by competitive GABA(A) receptor antagonists.

This paper considers the problem of epileptiform activity recognition in EEG of rats before and after Traumatic Brain Injury (TBI). Recognition and classification was based on expert markup of EEG signals with epileptiform activity - Epileptiform Discharges (ED) and normal sleep activity - Sleep Spindles (SS). Proprietary Event Detection Algorithm (EDA) based on time-frequency analysis of wavelet spectrograms was developed in order to extract valuable events from raw EEG records. Epilepsy Prediction Model (EPM) was based on Power Spectrum Density (PSD) and Frequency features of detected events. Resulted predictors were used in logistic regression model, which estimated probabilities of epileptiform activity in particular EEG event. Validation of proposed model was done by multiple train-test division. It was shown that the accuracy of prediction is around 80%. Proposed algorithms were applied for identification of epileptiform activity in long term EEG records of rats. It was proven that algorithms effectively distinguish epilepsy in rats after TBI in comparison with rats after False Surgery. Proposed approaches can be applied used for Post-Traumatic Epilepsy (PTE) diagnostics in the nearest future.

Background: The anticonvulsant effect of olfactory bulb (OB) and olfactory epithelium (OE) electrical stimulation was investigated in anesthetized and freely moving animals. Methods: Male Wistar rats were anesthetized with urethane (1.5 g/kg). Stimulating electrodes were bilaterally placed either in OB or OE. Another electrode was placed in the CA1 area for recording epileptiform discharges (EDs) following pentylenetetrazol (PTZ, i.v.) injection and evoked field potentials following Schaffer collateral stimulation. Rats were divided into PTZ and control groups. Each group received stimulation (1 Hz) either in OB (OBS) or OE (OES). ED threshold and duration, and the ability to generate long-term potentiation (LTP) were assessed. Finally, the effect of OBS on acute PTZ-induced seizure and working memory was investigated in freely moving animals. OBS significantly increased the ED threshold when applied at 250 µA and decreased ED duration when applied at 125 and 250 µA. Results: Applying OES had a small effect on the ED threshold but significantly decreased ED duration when applied at 125 and 250 µA. Both OBS and OES mitigated the PTZ-induced increase in basal synaptic transmission. Meanwhile, OBS and OES significantly restored the LTP generation following PTZ injection in anesthetized rats. In addition, applying OBS in freely moving animals reduced the seizure severity and restore working memory impairment. Conclusions Obtained data showed that the OB and OE may be considered as effective targets for electrical brain stimulation to attenuate epileptiform activity and seizure severity. In addition, both OBS and OES decreased the seizure-induced impairment in LTP generation.

To study the association between timing and characteristics of the first electroencephalography (EEG) with epileptiform discharges (ED-EEG) and epilepsy and neurodevelopment at 24months in infants with tuberous sclerosis complex (TSC). Patients enrolled in the prospective Epileptogenesis in a genetic model of epilepsy - Tuberous sclerosis complex (EPISTOP) trial, had serial EEG monitoring until the age of 24months. The timing and characteristics of the first ED-EEG were studied in relation to clinical outcome. Epilepsy-related outcomes were analyzed separately in a conventionally followed group (initiation of vigabatrin after seizure onset) and a preventive group (initiation of vigabatrin before seizures, but after appearance of interictal epileptiform discharges [IEDs]). Eighty-three infants with TSC were enrolled at a median age of 28days (interquartile range [IQR] 14-54). Seventy-nine of 83 patients (95%) developed epileptiform discharges at a median age of 77days (IQR 23-111). Patients with a pathogenic TSC2 variant were significantly younger (P-value .009) at first ED-EEG and more frequently had multifocal IED (P-value .042) than patients with a pathogenic TSC1 variant. A younger age at first ED-EEG was significantly associated with lower cognitive (P-value .010), language (P-value .001), and motor (P-value .013) developmental quotients at 24months. In the conventional group, 48 of 60 developed seizures. In this group, the presence of focal slowing on the first ED-EEG was predictive of earlier seizure onset (P-value .030). Earlier recording of epileptiform discharges (P-value .019), especially when multifocal (P-value .026) was associated with higher risk of drug-resistant epilepsy. In the preventive group, timing, distribution of IED, or focal slowing, was not associated with the epilepsy outcomes. However, when multifocal IEDs were present on the first ED-EEG, preventive treatment delayed the onset of seizures significantly (P-value <.001). Early EEG findings help to identify TSC infants at risk of severe epilepsy and neurodevelopmental delay and those who may benefit from preventive treatment with vigabatrin.

During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings to localize the epileptogenic focus. To increase the number of epileptiform discharges required for MEG analysis, methohexital a short-acting barbiturate that is known to activate epileptiform activity, was used. Additionally, we investigated the spike-provoking properties of clonidine in comparison to methohexital. After oral premedication with clonidine, short-lasting anesthesia was provided by intravenously administered methohexital. The number and location of epileptiform MEG discharges were assessed after clonidine premedication and during methohexital anesthesia. Results were compared with baseline MEG recordings. Methohexital increased the frequency of focal epileptiform discharges in eight of 13 patients (one of the 14 patients did not receive methohexital after premedication with clonidine). Additionally, premedication with clonidine was found to increase focal epileptiform discharges in nine of 14 patients. When compared with baseline MEG recordings, recordings after treatment with both clonidine premedication and methohexital anesthesia showed a significant increase in the total number of epileptiform signals and the number of spikes contributing to MEG source localizations. This study confirms the selective proconvulsant effects of methohexital on the epileptogenic focus as suggested previously by EEG and electrocorticogram (ECoG) investigations. Additionally, our data establish for the first time that clonidine increases epileptiform activity in patients with seizure disorders. These results indicate that clonidine is suited as an activating agent for the localization of epileptogenic foci by means of MEG. This effect of clonidine on specific epileptic activity also indicates that clonidine should be used with caution as an antihypertensive drug in patients with seizure disorders.

Levetiracetam reduces the frequency of interictal epileptiform discharges during NREM sleep in children with ADHD

In the current study, we investigated the effects of central asprosin administration on baseline brain activity and 4-aminopyridine (4-AP) induced epileptiform activity. Additionally, we examined the effects of asprosin on electrocorticography (ECoG) band powers. Forty-two male Wistar rats were divided into six groups as follows: sham, 4-AP (2.5mg/kg i.p.), asprosin 20 nmol (i.c.v.), asprosin 50 nmol (i.c.v.), asprosin 50 nmol (i.c.v.) posttreatment, and asprosin 50 nmol (i.c.v.) pre-treatment. Recordings lasting 60-70min were conducted for all groups under ketamine/xylazine (90/10mg/kg) anesthesia. In the posttreatment group, asprosin was injected 20min after the induction of epileptiform activity. In the pre-treatment group, asprosin was injected after baseline recordings, and following a 20-min pre-treatment period, 4-AP was administered. 4-AP alone induced epileptiform activity in all animals, peaking at approximately the 30th minute. Asprosin significantly reduced ECoG power at doses of 20 nmol and 50 nmol. Furthermore, both doses of asprosin reduced alpha, beta, delta, theta, and gamma band activity in ECoG recordings at various time points. However, asprosin pre- and posttreatment had no significant effect on 4-AP-induced epileptiform activity. These findings suggest that asprosin modulates cortical excitability under physiological conditions but is ineffective in attenuating induced epileptiform activity.

The aim of this prospective study was to determine the risk factors of epileptiform discharge during induction with sevoflurane in healthy adult patients. Forty adult patients with American Society of Anesthesiologists physical status I were randomly allocated to one of four groups. Group A: Patients breathed 8% sevoflurane in oxygen (8 l/min) via a prefilled circuit. End-tidal sevoflurane was maintained at 4%. Tracheal intubation was performed at the third minute after cisatracurium injection. Group B: The anesthesia protocol was similar, but a vital capacity technique was performed. Group C: Patients were anesthetized as in group A but were hyperventilated. Group D: Patients were anesthetized as in group A, but end-tidal sevoflurane was maintained at 2%. An electroencephalogram was recorded before and during induction up to 11 min after the start of induction. Statistical analysis was performed with Statview 5.0 (SAS Institute Inc., Cary, NC) for multivariate analysis. Twelve patients experienced epileptiform discharges. Risk factors were female sex (odds ratio, 12.60; 95% confidence interval, 1.46-135), delay to the occurrence of beta waves (odds ratio, 0.92; 95% confidence interval, 0.86-0.99), and end-tidal sevoflurane (odds ratio, 8.78; 95% confidence interval, 1.12-69). Epileptiform discharges were not associated with significant hemodynamic or Bispectral Index variations. Induction with sevoflurane may result in epileptiform electroencephalographic activity. Only electroencephalographic monitoring allows the diagnosis. Risk factors are mainly female sex, short delay to onset of anesthesia, and high alveolar sevoflurane concentration. Induction with high sevoflurane concentration is controversial mainly in women.

Detection of epileptiform discharges in the EEG by a hybrid system comprising mimetic, self-organized artificial neural network, and fuzzy logic stages

Given the ability to use the internet and applications that are both immediately accessible and highly rewarding to users, concern exists regarding the development of excessive and dysregulated smartphone use (also known as ‘smartphone addiction’). This chapter reviews the current state of research on dysregulated smartphone use, identifies gaps in the literature, and outlines future directions for research and practice. Dysregulated smartphone use is associated with a (1) significant loss of control over the behavior, resulting in (2) severe and persistent functional impairment in daily life. The most consistent correlates of dysregulated smartphone use include psychiatric symptoms and poor sleep health. Because there are few longitudinal studies with a rigorous methodology, it is not clear whether the correlates precede, co-occur with, or follow the onset of dysregulated smartphone use. Consistent conceptualization suggests that mental health problems could precede dysregulated smartphone use. Future research should seek to validate psychometrically sound screening instruments for dysregulated smartphone use in children and adolescents. Research on the longitudinal trajectories of dysregulated smartphone use and psychopathology, as well as physical health outcomes, is recommended. Given the high rates of smartphone ownership among children and young adolescents, clarifying how, and for whom, smartphone use interferes with functioning is critical.

Problematic smartphone use (PSU) is a growing concern that hurts users' daily lives and activities. Previous studies have emphasised the importance of developing mindfulness and self-efficacy concerning smartphone use rather than solely focussing on reducing usage. However, there has been little research developing and evaluating digital interventions specifically targeting absent-minded smartphone use. There is also little knowledge on how best mindfulness practice using digital technologies can be integrated with persuasive designs which have been widely studied and implemented for behaviour change. In this paper, we developed a live wallpaper application for Android lock and home screens as a mindfulness-based intervention for absent-minded smartphone use. The application was evaluated over two weeks with 121 participants. This was followed by a semi-structured interview with 15 participants. The results of our analysis show that the intervention reduced absent-minded smartphone use overall. While participants found the various features (especially the customisation features) of the intervention to be persuasive, we found no correlation between perceived persuasiveness and behaviour change. This work provides valuable insights for advancing human-computer interaction (HCI) research on PSU. Additionally, the results raise important questions for future research, such as the relationship between perceived persuasiveness and behaviour change. Finally, we contribute to the discussion on the applications of mindfulness in persuasive technology, challenges and future research areas.

Cardiac memory, also known as the Chatterjee phenomenon, refers to the persistent but reversible T-wave changes on ECG caused by an abnormal electrical activation pattern. After a period of abnormal ventricular activation in which the myocardial repolarization is altered and delayed (such as with artificial pacemakers, tachyarrhythmias with wide QRS complexes or ventricular pre-excitation), the heart remembers and mirrors its repolarization in the direction of the vector of "abnormally" activated QRS complexes. This phenomenon alters patterns of gap junction distribution and generates changes in repolarization seen at the level of ionic-channel, ionic concentrations, ionic-current gating and action potential. In this work, we propose a mathematical model of cardiac electrophysiology which takes into account cardiac memory phenomena. The electrical activity in heart through torso, which is dependent on the prior history of accrued heartbeats, is mathematically modeled by a modified bidomain system with time fractional-order dynamics (which are used to describe processes that exhibit memory). This new bidomain system, that I name "&lt;i&gt;it memory bidomain system&lt;/i&gt;", is a degenerate nonlinear coupled system of reaction-diffusion equations in shape of a fractional-order differential equation coupled with a set of time fractional-order partial differential equations. Cardiac memory is represented via fractional-order capacitor (associate to capacitive current) and fractional-order cellular membrane dynamics. First, mathematical model is introduced. Afterward, results on generalized Gronwall inequality within the framework of coupled fractional differential equations are developed. Next, the existence and uniqueness of solution of state system are proved as well as stability result. Further, some preliminary numerical applications are performed to show that memory reproduced by fractional-order derivatives can play a significant role on key dependent electrical properties including APD, action potential morphology and spontaneous activity.