8 research outputs found
Interictal Network Dynamics in Paediatric Epilepsy Surgery
Epilepsy is an archetypal brain network disorder. Despite two decades of research
elucidating network mechanisms of disease and correlating these with outcomes, the clinical
management of children with epilepsy does not readily integrate network concepts. For
example, network measures are not used in presurgical evaluation to guide decision making
or surgical management plans.
The aim of this thesis was to investigate novel network frameworks from the perspective of
a clinician, with the explicit aim of finding measures that may be clinically useful and
translatable to directly benefit patient care. We examined networks at three different scales,
namely macro (whole brain diffusion MRI), meso (subnetworks from SEEG recordings) and
micro (single unit networks) scales, consistently finding network abnormalities in children
being evaluated for or undergoing epilepsy surgery. This work also provides a path to clinical
translation, using frameworks such as IDEAL to robustly assess the impact of these new
technologies on management and outcomes.
The thesis sets up a platform from which promising computational technology, that utilises
brain network analyses, can be readily translated to benefit patient care
Advanced Invasive Neurophysiological Methods to Aid Decision Making in Paediatric Epilepsy Surgery
For patients with drug-resistant focal epilepsy, surgery is the most effective treatment to attain seizure freedom. Intracranial electroencephalogram investigations succeed in defining the seizure onset zone (SOZ) where non-invasive methods fail to identify a single seizure generator. However, resection of the SOZ does not always lead to a surgical benefit and, in addition, eloquent functions like language might be compromised. The aim of this thesis was to use advanced invasive neurophysiological methods to improve pre-surgical planning in two ways. The first aim was to improve delineation of the pathological tissue, the SOZ using novel quantitative neurophysiological biomarkers: high gamma activity (80â150Hz) phase-locked to low frequency iEEG discharges (phase-locked high gamma, PLHG) and high frequency oscillations called fast ripples (FR, 250â500Hz). Resection of contacts containing these markers were recently reported to lead to an improved seizure outcome. The current work shows the first replication of the PLHG metric in a small adult pilot study and a larger paediatric cohort. Furthermore, I tested whether surgical removal of PLHG- and/or FR-generating brain areas resulted in better outcome compared to the current clinical SOZ delineation. The second aim of this work was to aid delineation of eloquent language cortex. Invasive event-related potentials (iERP) and spectral changes in the beta and gamma frequency bands were used to determine cortical dynamics during speech perception and production across widespread brain regions. Furthermore, the relationship between these cortical dynamics and the relationship to electrical stimulation responses was explored. For delineation of pathological tissue, the combination of FRs and SOZ proved to be a promising biomarker. Localising language cortex showed the highest level of activity around the perisylvian brain regions with a significantly higher occurrence rate of iERPs compared to spectral changes. Concerning electrical stimulation mapping beta and high gamma frequency bands represented the most promising markers
Towards Accurate Forecasting of Epileptic Seizures: Artificial Intelligence and Effective Connectivity Findings
LâĂ©pilepsie est une des maladies neurologiques les plus frĂ©quentes, touchant prĂšs dâun
pourcent de la population mondiale. De nos jours, bien quâenviron deux tiers des patients
Ă©pileptiques rĂ©pondent adĂ©quatement aux traitements pharmacologiques, il reste quâun tiers des
patients doivent vivre avec des crises invalidantes et imprévisibles. Quoique la chirurgie
dâĂ©pilepsie puisse ĂȘtre une autre option thĂ©rapeutique envisageable, le recours Ă la chirurgie de
résection demeure trÚs faible en partie pour des raisons diverses (taux de réussite modeste, peur
des complications, perceptions nĂ©gatives). Dâautres avenues de traitement sont donc souhaitables.
Une piste actuellement explorĂ©e par des groupes de chercheurs est de tenter de prĂ©dire les crises Ă
partir dâenregistrements de lâactivitĂ© cĂ©rĂ©brale des patients. La capacitĂ© de prĂ©dire la survenue de
crises permettrait notamment aux patients, aidants naturels ou personnels médical de prendre des
mesures de prĂ©caution pour Ă©viter les dĂ©sagrĂ©ments reliĂ©s aux crises voire mĂȘme instaurer un
traitement pour les faire avorter. Au cours des derniĂšres annĂ©es, dâimportants efforts ont Ă©tĂ©
dĂ©ployĂ©s pour dĂ©velopper des algorithmes de prĂ©diction de crises et dâen amĂ©liorer les
performances.
Toutefois, le manque dâenregistrements Ă©lectroencĂ©phalographiques intracrĂąniens (iEEG) de
longue durée de qualité, la quantité limitée de crises, ainsi que la courte durée des périodes
interictales constituaient des obstacles majeurs à une évaluation adéquate de la performance des
algorithmes de prĂ©diction de crises. RĂ©cemment, la disponibilitĂ© en ligne dâenregistrements iEEG
continus avec échantillonnage bilatéral (des deux hémisphÚres) acquis chez des chiens atteints
dâĂ©pilepsie focale Ă lâaide du dispositif de surveillance ambulatoire implantable NeuroVista a
partiellement facilitĂ© cette tĂąche. Cependant, une des limitations associĂ©es Ă lâutilisation de ces
donnĂ©es durant la conception dâun algorithme de prĂ©diction de crises Ă©tait lâabsence
dâinformation concernant la zone exacte de dĂ©but des crises (information non fournie par les
gestionnaires de cette base de données en ligne). Le premier objectif de cette thÚse était la mise
en oeuvre dâun algorithme prĂ©cis de prĂ©diction de crises basĂ© sur des enregistrements iEEG canins
de longue durée. Les principales contributions à cet égard incluent une localisation quantitative
de la zone dâapparition des crises (basĂ©e sur la fonction de transfert dirigĂ© âDTF), lâutilisation
dâune nouvelle fonction de coĂ»t via lâalgorithme gĂ©nĂ©tique proposĂ©, ainsi quâune Ă©valuation
quasi-prospective des performances de prĂ©diction (donnĂ©es de test dâun total de 893 jours). Les rĂ©sultats ont montrĂ© une amĂ©lioration des performances de prĂ©diction par rapport aux Ă©tudes
antérieures, atteignant une sensibilité moyenne de 84.82 % et un temps en avertissement de 10 %.
La DTF, utilisée précédemment comme mesure de connectivité pour déterminer le réseau
épileptique (objectif 1), a été préalablement validée pour quantifier les relations causales entre les
canaux lorsque les exigences de quasi-stationnarité sont satisfaites. Ceci est possible dans le cas
des enregistrements canins en raison du nombre relativement faible de canaux. Pour faire face
aux exigences de non-stationnarité, la fonction de transfert adaptatif pondérée par le spectre
(Spectrum weighted adaptive directed transfer function - swADTF) a Ă©tĂ© introduit en tant quâune
version variant dans le temps de la DTF. Le second objectif de cette thĂšse Ă©tait de valider la
possibilitĂ© dâidentifier les endroits Ă©metteurs (ou sources) et rĂ©cepteurs dâactivitĂ© Ă©pileptiques en
appliquant la swADTF sur des enregistrements iEEG de haute densité provenant de patients
admis pour Ă©valuation prĂ©-chirurgicale au CHUM. Les gĂ©nĂ©rateurs dâactivitĂ© Ă©pileptique Ă©taient
dans le volume réséqué pour les patients ayant des bons résultats post-chirurgicaux alors que
différents foyers ont été identifiés chez les patients ayant eu de mauvais résultats postchirurgicaux.
Ces rĂ©sultats dĂ©montrent la possibilitĂ© dâune identification prĂ©cise des sources et
rĂ©cepteurs dâactivitĂ©s Ă©pileptiques au moyen de la swADTF ouvrant la porte Ă la possibilitĂ© dâune
meilleure sĂ©lection dâĂ©lectrodes de maniĂšre quantitative dans un contexte de dĂ©veloppement
dâalgorithme de prĂ©diction de crises chez lâhumain.
Dans le but dâexplorer de nouvelles avenues pour la prĂ©diction de crises Ă©pileptiques, un
nouveau prĂ©curseur a aussi Ă©tĂ© Ă©tudiĂ© combinant lâanalyse des spectres dâordre supĂ©rieur et les
réseaux de neurones artificiels (objectif 3). Les résultats ont montré des différences
statistiquement significatives (p<0.05) entre lâĂ©tat prĂ©ictal et lâĂ©tat interictal en utilisant chacune
des caractéristiques extraites du bi-spectre. Utilisées comme entrées à un perceptron multicouche,
lâentropie bispectrale normalisĂ©e, lâentropie carrĂ© normalisĂ©e, et la moyenne ont atteint des
précisions respectives de 78.11 %, 72.64% et 73.26%.
Les résultats de cette thÚse confirment la faisabilité de prédiction de crises à partir
dâenregistrements dâĂ©lectroencĂ©phalographie intracrĂąniens. Cependant, des efforts
supplĂ©mentaires en termes de sĂ©lection dâĂ©lectrodes, dâextraction de caractĂ©ristiques, dâutilisation
des techniques dâapprentissage profond et dâimplĂ©mentation Hardware, sont nĂ©cessaires avant
lâintĂ©gration de ces approches dans les dispositifs implantables commerciaux.----------ABSTRACT
Epilepsy is a chronic condition characterized by recurrent âunpredictableâ seizures. While
the first line of treatment consists of long-term drug therapy about one-third of patients are said to
be pharmacoresistant. In addition, recourse to epilepsy surgery remains low in part due to
persisting negative attitudes towards resective surgery, fear of complications and only moderate
success rates. An important direction of research is to investigate the possibility of predicting
seizures which, if achieved, can lead to novel interventional avenues.
The paucity of intracranial electroencephalography (iEEG) recordings, the limited number of
ictal events, and the short duration of interictal periods have been important obstacles for an
adequate assessment of seizure forecasting. More recently, long-term continuous bilateral iEEG
recordings acquired from dogs with naturally occurring focal epilepsy, using the implantable
NeuroVista ambulatory monitoring device have been made available on line for the benefit of
researchers. Still, an important limitation of these recordings for seizure-prediction studies was
that the seizure onset zone was not disclosed/available. The first objective of this thesis was to
develop an accurate seizure forecasting algorithm based on these canine ambulatory iEEG
recordings. Main contributions include a quantitative, directed transfer function (DTF)-based,
localization of the seizure onset zone (electrode selection), a new fitness function for the
proposed genetic algorithm (feature selection), and a quasi-prospective assessment of seizure
forecasting on long-term continuous iEEG recordings (total of 893 testing days). Results showed
performance improvement compared to previous studies, achieving an average sensitivity of
84.82% and a time in warning of 10 %.
The DTF has been previously validated for quantifying causal relations when quasistationarity
requirements are met. Although such requirements can be fulfilled in the case of
canine recordings due to the relatively low number of channels (objective 1), the identification of
stationary segments would be more challenging in the case of high density iEEG recordings. To
cope with non-stationarity issues, the spectrum weighted adaptive directed transfer function
(swADTF) was recently introduced as a time-varying version of the DTF. The second objective
of this thesis was to validate the feasibility of identifying sources and sinks of seizure activity
based on the swADTF using high-density iEEG recordings of patients admitted for pre-surgical monitoring at the CHUM. Generators of seizure activity were within the resected volume for
patients with good post-surgical outcomes, whereas different or additional seizure foci were
identified in patients with poor post-surgical outcomes. Results confirmed the possibility of
accurate identification of seizure origin and propagation by means of swADTF paving the way
for its use in seizure prediction algorithms by allowing a more tailored electrode selection.
Finally, in an attempt to explore new avenues for seizure forecasting, we proposed a new
precursor of seizure activity by combining higher order spectral analysis and artificial neural
networks (objective 3). Results showed statistically significant differences (p<0.05) between
preictal and interictal states using all the bispectrum-extracted features. Normalized bispectral
entropy, normalized squared entropy and mean of magnitude, when employed as inputs to a
multi-layer perceptron classifier, achieved held-out test accuracies of 78.11%, 72.64%, and
73.26%, respectively.
Results of this thesis confirm the feasibility of seizure forecasting based on iEEG recordings;
the transition into the ictal state is not random and consists of a âbuild-upâ, leading to seizures.
However, additional efforts in terms of electrode selection, feature extraction, hardware and deep
learning implementation, are required before the translation of current approaches into
commercial devices
Influence of deep structures on the EEG and their invasive and non-invasive assessment
Tesis inĂ©dita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de FisiologĂa, leĂda el 22-11-2019El EEG es la prueba diagnĂłstica de mayor utilidad en el diagnĂłstico de la epilepsia. Consiste esencialmente en la representaciĂłn grĂĄfica de los potenciales postsinĂĄpticos generados en las neuronas piramidales de la corteza. Los campos elĂ©ctricos registrados en la superficie tienen principalmente dos mecanismos de origen: conducciĂłn de volumen desde regiones adyacentes y propagaciĂłn interneuronal sinĂĄptica. Las neuronal piramidales se agrupan formando microcircuitos locales siendo estos circuitos los responsables de la generaciĂłn delos ritmos registrados en el EEG. Uno de los principales retos de la electroencefalografĂa consiste en descifrar la relaciĂłn entre la actividad registrada y la actividad subyacente en las redes neuronales. Para encontrar la fuente de dichas actividades, es necesario tener en cuenta complejos mecanismos tanto no lineales como lineales, asĂ como el efecto de la conducciĂłn de volumen y la influencia de la morfologĂa y las propiedades elĂ©ctricas del cerebro y el crĂĄneo. AdemĂĄs, las regiones cerebrales se encuentran profusamente interconectadas a menudo produciendo una modulaciĂłn recĂproca que añade un mayor grado complejidad...The EEG is the most valuable diagnostic test in epilepsy. In essence, it mainly consists in agraphical representation of the summated postsynaptic potentials generated in the pyramidal neurons from the cortex. The electrical fields can be generated on the scalp by two mechanisms: volume conduction from nearby regions and synaptic interâneuronal propagation. Pyramidal cells align conforming local microcircuit configurations which activation lead to the generation of EEG rhythms. One of the main challenges of EEG is to decipher the relation between the recorded EEG activity and the activity in the neuronal networks. To find the source of EEG activity, complex nonâlinear and linear mechanisms as well as volume conduction effect and influence of the shape and electrical properties of the brain and skull need to be taken in consideration. In addition, brain regions are profusely interconnected and functionally connected regions often produce mutual modulation that adds additional complexity...Depto. de FisiologĂaFac. de MedicinaTRUEunpu
Simulation and implementation of novel deep learning hardware architectures for resource constrained devices
Corey Lammie designed mixed signal memristive-complementary metalâoxideâsemiconductor (CMOS) and field programmable gate arrays (FPGA) hardware architectures, which were used to reduce the power and resource requirements of Deep Learning (DL) systems; both during inference and training. Disruptive design methodologies, such as those explored in this thesis, can be used to facilitate the design of next-generation DL systems