Design of a Simulator for Neonatal Multichannel EEG: Application to Time-Frequency Approaches for Automatic Artifact Removal and Seizure Detection

The electroencephalogram (EEG) is used to noninvasively monitor brain activities; it is the most utilized tool to detect abnormalities such as seizures. In recent studies, detection of neonatal EEG seizures has been automated to assist neurophysiologists in diagnosing EEG as manual detection is time consuming and subjective; however it still lacks the necessary robustness that is required for clinical implementation. Moreover, as EEG is intended to record the cerebral activities, extra-cerebral activities external to the brain are also recorded; these are called “artifacts” and can seriously degrade the accuracy of seizure detection. Seizures are one of the most common neurologic problems managed by hospitals occurring in 0.1%-0.5% livebirths. Neonates with seizures are at higher risk for mortality and are reported to be 55-70 times more likely to have severe cerebral-palsy. Therefore, early and accurate detection of neonatal seizures is important to prevent long-term neurological damage. Several attempts in modelling the neonatal EEG and artifacts have been done, but most did not consider the multichannel case. Furthermore, these models were used to test artifact or seizure detection separately, but not together. This study aims to design synthetic models that generate clean or corrupted multichannel EEG to test the accuracy of available artifact and seizure detection algorithms in a controlled environment. In this thesis, synthetic neonatal EEG model is constructed by using; single-channel EEG simulators, head model, 21-electrodes, and propagation equations, to produce clean multichannel EEG. Furthermore, neonatal EEG artifact model is designed using synthetic signals to corrupt EEG waveforms. After that, an automated EEG artifact detection and removal system is designed in both time and time-frequency domains. Artifact detection is optimised and removal performance is evaluated. Finally, an automated seizure detection technique is developed, utilising fused and extended multichannel features along a cross-validated SVM classifier. Results show that the synthetic EEG model mimics real neonatal EEG with 0.62 average correlation, and corrupted-EEG can degrade seizure detection average accuracy from 100% to 70.9%. They also show that using artifact detection and removal enhances the average accuracy to 89.6%, and utilising the extended features enhances it to 97.4% and strengthened its robustness.لمراقبة ورصد أنشطة واشارات المخ، دون الحاجة لأي عملیات (EEG) یستخدم الرسم أو التخطیط الكھربائي للدماغ للدماغجراحیة، وھي تعد الأداة الأكثر استخداما في الكشف عن أي شذوذأو نوبات غیر طبیعیة مثل نوبات الصرع. وقد أظھرت دراسات حدیثة، أن الكشف الآلي لنوبات حدیثي الولادة، ساعد علماء الفسیولوجیا العصبیة في تشخیص الاشارات الدماغیة بشكل أكبر من الكشف الیدوي، حیث أن الكشف الیدوي یحتاج إلى وقت وجھد أكبر وھوذو فعالیة أقل بكثیر، إلا أنھ لا یزال یفتقر إلى المتانة الضروریة والمطلوبة للتطبیق السریري.علاوة على ذلك؛ فكما یقوم الرسم الكھربائي بتسجیل الأنشطة والإشارات الدماغیة الداخلیة، فھو یسجل أیضا أي نشاط أو اشارات خارجیة، مما یؤدي إلى -(artifacts) :حدوث خلل في مدى دقة وفعالیة الكشف عن النوبات الدماغیة الداخلیة، ویطلق على تلك الاشارات مسمى (نتاج صنعي) . 0.5٪ولادة حدیثة في -٪تعد نوبات الصرع من أكثر المشكلات العصبیة انتشارا،ً وھي تصیب ما یقارب 0.1المستشفیات. حیث أن حدیثي الولادة المصابین بنوبات الصرع ھم أكثر عرضة للوفاة، وكما تشیر التقاریر الى أنھم 70مرة أكثر. لذا یعد الكشف المبكر والدقیق للنوبات الدماغیة -معرضین للإصابة بالشلل الدماغي الشدید بما یقارب 55لحدیثي الولادة مھم جدا لمنع الضرر العصبي على المدى الطویل. لقد تم القیام بالعدید من المحاولات التي كانتتھدف الى تصمیم نموذج التخطیط الكھربائي والنتاج الصنعي لدماغ حدیثي الولادة, إلا أن معظمھا لم یعر أي اھتمام الى قضیة تعدد القنوات. إضافة الى ذلك, استخدمت ھذه النماذج , كل على حدة, أو نوبات الصرع. تھدف ھذه الدراسة الى تصمیم نماذج مصطنعة من شأنھا (artifact) لإختبار كاشفات النتاج الصنعيأن تولد اشارات دماغیة متعددة القنوات سلیمة أو معطلة وذلك لفحص مدى دقة فعالیة خوارزمیات الكشف عن نوبات ضمن بیئة یمكن السیطرة علیھا. (artifact) الصرع و النتاج الصنعي في ھذه الأطروحة, یتكون نموذج الرسم الكھربائي المصطنع لحدیثي الولادة من : قناة محاكاة واحده للرسم الكھربائي, نموذج رأس, 21قطب كھربائي و معادلات إنتشار. حیث تھدف جمیعھا لإنتاج إشاراة سلیمة متعدده القنوات للتخطیط عن طریق استخدام اشارات مصطنعة (artifact) الكھربائي للدماغ.علاوة على ذلك, لقد تم تصمیم نموذجالنتاج الصنعيفي نطاقالوقت و (artifact) لإتلاف الرسم الكھربائي للدماغ. بعد ذلك تم انشاء برنامج لكشف و إزالةالنتاج الصناعينطاقالوقت و التردد المشترك. تم تحسین برنامج الكشف النتاج الصناعيالى ابعد ما یمكن بینما تمت عملیة تقییم أداء الإزالة. وفي الختام تم التمكن من تطویر تقنیة الكشف الآلي عن نوبات الصرع, وذلك بتوظیف صفات مدمجة و صفات الذي تم التأكد من صحتھ. (SVM) جدیدة للقنوات المتعددة لإستخدامھا للمصنفلقد أظھرت النتائج أن نموذج الرسم الكھربائي المصطنع لحدیثي الولادة یحاكي الرسمالكھربائي الحقیقي لحدیثي الولادة بمتوسط ترابط 0.62, و أنالرسم الكھربائي المتضرر للدماغ قد یؤدي الى حدوث ھبوطفي مدى دقة متوسط الكشف عن نوبات الصرع من 100%الى 70.9%. وقد أشارت أیضا الى أن استخدام الكشف والإزالة عن النتاج الصنعي (artifact) یؤدي الى تحسن مستوى الدقة الى نسبة 89.6 %, وأن توظیف الصفات الجدیدة للقنوات المتعددة یزید من تحسنھا لتصل الى نسبة 94.4 % مما یعمل على دعم متانتھا

Vauvojen unen luokittelu patja-sensorilla ja EKG:lla

Infants spend the majority of their time asleep. Although extensive studies have been carried out, the role of sleep for infant cognitive, psychomotor, temperament and developmental outcomes is not clear. The current contradictory results may be due to the limited precision when monitoring infant sleep for prolonged periods of time, from weeks to even months. Sleep-wake cycle can be assessed with sleep questionnaires and actigraphy, but they cannot separate sleep stages. The gold standard for sleep state annotation is polysomnography (PSG), which consist of several signal modalities such as electroencephalogram, electrooculogram, electrocardiogram (ECG), electromyogram, respiration sensor and pulse oximetry. A sleep clinician manually assigns sleep stages for 30 sec epochs based on the visual observation of these signals. Because method is obtrusive and laborious it is not suitable for monitoring long periods. There is, therefore, a need for an automatic and unobtrusive sleep staging approach. In this work, a set of classifiers for infant sleep staging was created and evaluated. The cardiorespiratory and gross body movement signals were used as an input. The different classifiers aim to distinguish between two or more different sleep states. The classifiers were built on a clinical sleep polysomnography data set of 48 infants with ages ranging from 1 week to 18 weeks old (a median of 5 weeks). Respiration and gross body movements were observed using an electromechanical film bed mattress sensor manufactured by Emfit Ltd. ECG of the PSG setup was used for extracting cardiac activity. Signals were preprocessed to remove artefacts and an extensive set of features (N=81) were extracted on which the classifiers were trained. The NREM3 vs other states classifier provided the most accurate results. The median accuracy was 0.822 (IQR: 0.724-0.914). This is comparable to previously published studies on other sleep classifiers, as well as to the level of clinical interrater agreement. Classification methods were confounded by the lack of muscle atonia and amount of gross body movements in REM sleep. The proposed method could be readily applied for home monitoring, as well as for monitoring in neonatal intensive care units.Vauvat nukkuvat suurimman osan vuorokaudesta. Vaikkakin laajasti on tutkittu unen vaikutusta lapsen kognitioon, psykomotoriikkaan, temperamenttiin ja kehitykseen, selkeää kuvaa ja yhtenäistä konsensusta tiedeyhteisössä ei ole saavutettu. Yksi syy tähän on että ei ole olemassa menetelmää, joka soveltuisi jatkuva-aikaiseen ja pitkäkestoiseen unitilan monitorointiin. Vauvojen uni-valve- sykliä voidaan selvittää vanhemmille suunnatuilla kyselyillä ja aktigrafialla, mutta näillä ei voi havaita unitilojen rakennetta. Kliinisenä standardina unitilojen seurannassa on polysomnografia, jossa samanaikaisesti mitataan mm. potilaan elektroenkelografiaa, elektro-okulografiaa, elektrokardiografiaa, electromyografiaa, hengitysinduktiivisesta pletysmografiaa, happisaturaatiota ja hengitysvirtauksia. Kliinikko suorittaa univaiheluokittelun signaaleista näkyvien, vaiheille tyypillisten, hahmojen perusteella. Työläyden ja häiritsevän mittausasetelman takia menetelmä ei sovellu pitkäaikaiseen seurantaan. On tarvetta kehittää tarkoitukseen sopivia automaattisia ja huomaamattomia unenseurantamenetelmiä. Tässä työssä kehitettiin ja testattiin sydämen syke-, hengitys ja liikeanalyysiin perustuvia koneluokittimia vauvojen unitilojen havainnointiin. Luokittimet opetettiin kliinisessa polysomnografiassa kerätyllä datalla 48 vauvasta, joiden ikä vaihteli 1. viikosta 18. viikkoon (mediaani 5 viikkoa). Vauvojen hengitystä ja liikkeitä seurattiin Emfit Oy:n valmistamalla elektromekaaniseen filmiin pohjatuvalla patja-sensorilla. Lisäksi ECG:lla seurattiin sydäntä ja opetuksessa käytettiin lääkärin suorittamaa PSG-pohjaista luokitusta. Esikäsittelyn jälkeen signaaleista laskettiin suuri joukko piirrevektoreita (N=81), joihin luokittelu perustuu. NREM3-univaiheen tunnistus onnistui parhaiten 0.822 mediaani-tarkkuudella ja [0.724,0.914] kvartaaleilla. Tulos on yhtenevä kirjallisuudessa esitettyjen arvojen kanssa ja vastaa kliinikkojen välistä toistettavuutta. Muilla luokittimilla univaiheet sekoituivat keskenään, mikä on oletattavasti selitettävissä aikuisista poikeavalla REM-unen aikaisella lihasjäykkyydellä ja kehon liikkeillä. Työ osoittaa, että menetelmällä voi seurata vauvojen uniluokkien oskillaatiota. Järjestelmää voisi käyttää kotiseurannassa tai vastasyntyneiden teholla unenvalvontaan

Toward a personalized real-time diagnosis in neonatal seizure detection

The problem of creating a personalized seizure detection algorithm for newborns is tackled in this paper. A probabilistic framework for semi-supervised adaptation of a generic patient-independent neonatal seizure detector is proposed. A system that is based on a combination of patient-adaptive (generative) and patient-independent (discriminative) classifiers is designed and evaluated on a large database of unedited continuous multichannel neonatal EEG recordings of over 800 h in duration. It is shown that an improvement in the detection of neonatal seizures over the course of long EEG recordings is achievable with on-the-fly incorporation of patient-specific EEG characteristics. In the clinical setting, the employment of the developed system will maintain a seizure detection rate at 70% while halving the number of false detections per hour, from 0.4 to 0.2 FD/h. This is the first study to propose the use of online adaptation without clinical labels, to build a personalized diagnostic system for the detection of neonatal seizures

Spontaanien aktiviteettipurskeiden automaattinen tunnistus keskosten aivosähkökäyrästä

Very preterm infants may require neonatal intensive care for several months, and the developmental outcome of the care depends on how well brain function can be managed. Direct monitoring of brain function with electroencephalography (EEG) is currently not a part of routine care, since it is perceived challenging due to difficulties in its interpretation. Therefore, automated methods for EEG interpretation are needed in order to make brain monitoring part of the routine in neonatal intensive care. This thesis investigates the detection of spontaneous activity transients (SATs), which form the majority of brain activity in preterm infants. Using manual markings by three doctors in 18 short recordings of preterm EEG, I show that SATs can be recognized by doctors in a consistent manner. A commercially available algorithm is then tested for its ability to detect SATs automatically. The performance of the algorithm is clearly insufficient and therefore it is developed further. The parameters of the new, streamlined algorithm are optimized using unanimous markings by the three doctors as a gold standard. Estimates for the performance of the algorithm on unseen data are obtained by running the optimization 18 times, each time leaving out one of the recordings. The algorithm is then run on the EEG left out from the optimization using the optimized parameters. The estimated performance of the algorithm is found to be excellent, with sensitivity of 96.6 +- 2.8 % and specificity of 95.1 +- 5.6 %. Segmentation of the EEG into SATs and periods between SATs is a starting point for further analysis. One promising direction for future studies is to use SAT%, the proportion of time covered by SATs, to detect cycles of different vigilance stages in preterm infants. Such cyclicity could become a marker of the brain's wellbeing. The algorithm presented in this thesis may contribute to better care of preterm infants.Erittäin ennenaikaisesti syntyneet keskoset saattavat tarvita teho-osastohoitoa jopa kuukausien ajan. Hoidon vaikutus lapsen kehitykseen riippuu paljon siitä, kuinka hyvin aivojen hoito onnistuu. Aivojen toiminnan jatkuva valvonta elektroenkefalografian (EEG) avulla ei vielä kuulu tavanomaiseen hoitokäytäntöön, koska EEG:n tulkintaa pidetään vaikeana. EEG:n tulkintaan tarvitaankin automaattisia menetelmiä, jotta aivojen tarkkailusta tulisi osa vastasyntyneiden tehohoidon rutiinia. Tässä työssä tutkitaan spontaanien aktiviteettipurskeiden tunnistamista (engl. spontaneous activity transient, SAT). Keskosten aivotoiminta muodostuu suurelta osin aktiviteettipurskeista. Käyttämällä kolmen lääkärin käsin tehtyjä merkintöjä aktiviteettipurskeista 18 lyhyessä keskosilta mitatussa EEG:ssä todistan, että lääkärit tunnistavat aktiviteettipurskeet johdonmukaisesti. Tämän jälkeen testaan, sopiiko eräs myynnissä oleva algoritmi aktiviteettipurskeiden automaattiseen tunnistukseen. Algoritmin suorituskyky ei ole riittävä, joten kehitän siitä paremman version. Uuden, parannellun algoritmin parametrit optimoidaan käyttämällä opetusaineistona niitä EEGjaksoja, joiden luokittelusta kaikki kolme lääkäriä olivat yhtä mieltä. Algoritmin suorituskykyä arvioidaan suorittamalla optimointi 18 kertaa siten, että kullakin kerralla yksi mittauksista jätetään pois opetusaineistosta. Optimoitua menetelmää käytetään sitten aktiviteettipurskeiden tunnistamiseen poisjätetyssä mittauksessa. Algoritmin arvioitu suorituskyky on erinomainen; sen sensitiivisyys on 96,6 +- 2,8 % ja spesifisyys 95,1 +- 5,6 %. EEG:n segmentointi aktiviteettipurskeisiin ja niiden välisiin jaksoihin tarjoaa pohjan jatkoanalyysille. Aktiviteettipurskeiden osuutta EEG:stä (SAT%) voidaan mahdollisesti käyttää keskosen vireystilan vaihtelujen seuraamiseen. Vireystilojen säännöllinen vaihtelu saattaa olla merkki aivojen hyvinvoinnista. Tässä työssä esitelty algoritmi voi osaltaan edesauttaa keskosten hoidon kehittymistä entistä paremmaksi

Advances toward precision therapeutics for developmental and epileptic encephalopathies

Developmental and epileptic encephalopathies are childhood syndromes of severe epilepsy associated with cognitive and behavioral disorders. Of note, epileptic seizures represent only a part, although substantial, of the clinical spectrum. Whether the epileptiform activity per se accounts for developmental and intellectual disabilities is still unclear. In a few cases, seizures can be alleviated by antiseizure medication (ASM). However, the major comorbid features associated remain unsolved, including psychiatric disorders such as autism-like and attention deficit hyperactivity disorder-like behavior. Not surprisingly, the number of genes known to be involved is continuously growing, and genetically engineered rodent models are valuable tools for investigating the impact of gene mutations on local and distributed brain circuits. Despite the inconsistencies and problems arising in the generation and validation of the different preclinical models, those are unique and precious tools to identify new molecular targets, and essential to provide prospects for effective therapeutics

Epilepsy

With the vision of including authors from different parts of the world, different educational backgrounds, and offering open-access to their published work, InTech proudly presents the latest edited book in epilepsy research, Epilepsy: Histological, electroencephalographic, and psychological aspects. Here are twelve interesting and inspiring chapters dealing with basic molecular and cellular mechanisms underlying epileptic seizures, electroencephalographic findings, and neuropsychological, psychological, and psychiatric aspects of epileptic seizures, but non-epileptic as well

Neurodevelopmental disorders: 2021 update

One of the current challenges in the field of neurodevelopmental disorders (NDDs) is still to determine their underlying aetiology and risk factors. NDDs comprise a diverse group of disorders primarily related to neuro-developmental dysfunction including autism spectrum disorder (ASD), developmental delay, intellectual dis-ability (ID), and attention-deficit/hyperactivity disorder (ADHD) that may present with a certain degree of cognitive dysfunction and high prevalence of neuropsychiatric outcomes. Last year, advances in human ge-nomics have begun to shed light on the genetic architecture of these disorders and large-scale sequencing studies are starting to reveal mechanisms that range from unique genomic DNA methylation patterns (i.e. “episignatures”) to highly polygenic conditions. In addition, the contribution of de novo somatic mutations to neurodevelopmental diseases is being recognized. However, progressing from genetic findings to underlying neuropathological mechanisms has proved challenging, due to the increased resolution of the molecular and genetic assays. Advancement in modelling tools is likely to improve our understanding of the origin of neuro-developmental disorders and provide insight into their developmental mechanisms. Also, combined in vivo editing of multiple genes and single-cell RNA-sequencing (scRNA-seq) are bringing us into a new era of un-derstanding the molecular neuropathology of NDDs