Automatic Detection of Dementia and related Affective Disorders through Processing of Speech and Language

In 2019, dementia is has become a trillion dollar disorder. Alzheimer’s disease (AD) is a type of dementia in which the main observable symptom is a decline in cognitive functions, notably memory, as well as language and problem-solving. Experts agree that early detection is crucial to effectively develop and apply interventions and treatments, underlining the need for effective and pervasive assessment and screening tools. The goal of this thesis is to explores how computational techniques can be used to process speech and language samples produced by patients suffering from dementia or related affective disorders, to the end of automatically detecting them in large populations us- ing machine learning models. A strong focus is laid on the detection of early stage dementia (MCI), as most clinical trials today focus on intervention at this level. To this end, novel automatic and semi-automatic analysis schemes for a speech-based cogni- tive task, i.e., verbal fluency, are explored and evaluated to be an appropriate screening task. Due to a lack of available patient data in most languages, world-first multilingual approaches to detecting dementia are introduced in this thesis. Results are encouraging and clear benefits on a small French dataset become visible. Lastly, the task of detecting these people with dementia who also suffer from an affective disorder called apathy is explored. Since they are more likely to convert into later stage of dementia faster, it is crucial to identify them. These are the fist experiments that consider this task us- ing solely speech and language as inputs. Results are again encouraging, both using only speech or language data elicited using emotional questions. Overall, strong results encourage further research in establishing speech-based biomarkers for early detection and monitoring of these disorders to better patients’ lives.Im Jahr 2019 ist Demenz zu einer Billionen-Dollar-Krankheit geworden. Die Alzheimer- Krankheit (AD) ist eine Form der Demenz, bei der das Hauptsymptom eine Abnahme der kognitiven Funktionen ist, insbesondere des Gedächtnisses sowie der Sprache und des Problemlösungsvermögens. Experten sind sich einig, dass eine frühzeitige Erkennung entscheidend für die effektive Entwicklung und Anwendung von Interventionen und Behandlungen ist, was den Bedarf an effektiven und durchgängigen Bewertungsund Screening-Tools unterstreicht. Das Ziel dieser Arbeit ist es zu erforschen, wie computergest ützte Techniken eingesetzt werden können, um Sprach- und Sprechproben von Patienten, die an Demenz oder verwandten affektiven Störungen leiden, zu verarbeiten, mit dem Ziel, diese in großen Populationen mit Hilfe von maschinellen Lernmodellen automatisch zu erkennen. Ein starker Fokus liegt auf der Erkennung von Demenz im Frühstadium (MCI), da sich die meisten klinischen Studien heute auf eine Intervention auf dieser Ebene konzentrieren. Zu diesem Zweck werden neuartige automatische und halbautomatische Analyseschemata für eine sprachbasierte kognitive Aufgabe, d.h. die verbale Geläufigkeit, erforscht und als geeignete Screening-Aufgabe bewertet. Aufgrund des Mangels an verfügbaren Patientendaten in den meisten Sprachen werden in dieser Arbeit weltweit erstmalig mehrsprachige Ansätze zur Erkennung von Demenz vorgestellt. Die Ergebnisse sind ermutigend und es werden deutliche Vorteile an einem kleinen französischen Datensatz sichtbar. Schließlich wird die Aufgabe untersucht, jene Menschen mit Demenz zu erkennen, die auch an einer affektiven Störung namens Apathie leiden. Da sie mit größerer Wahrscheinlichkeit schneller in ein späteres Stadium der Demenz übergehen, ist es entscheidend, sie zu identifizieren. Dies sind die ersten Experimente, die diese Aufgabe unter ausschließlicher Verwendung von Sprache und Sprache als Input betrachten. Die Ergebnisse sind wieder ermutigend, sowohl bei der Verwendung von reiner Sprache als auch bei der Verwendung von Sprachdaten, die durch emotionale Fragen ausgelöst werden. Insgesamt sind die Ergebnisse sehr ermutigend und ermutigen zu weiterer Forschung, um sprachbasierte Biomarker für die Früherkennung und Überwachung dieser Erkrankungen zu etablieren und so das Leben der Patienten zu verbessern

Ontology Enrichment from Free-text Clinical Documents: A Comparison of Alternative Approaches

While the biomedical informatics community widely acknowledges the utility of domain ontologies, there remain many barriers to their effective use. One important requirement of domain ontologies is that they achieve a high degree of coverage of the domain concepts and concept relationships. However, the development of these ontologies is typically a manual, time-consuming, and often error-prone process. Limited resources result in missing concepts and relationships, as well as difficulty in updating the ontology as domain knowledge changes. Methodologies developed in the fields of Natural Language Processing (NLP), Information Extraction (IE), Information Retrieval (IR), and Machine Learning (ML) provide techniques for automating the enrichment of ontology from free-text documents. In this dissertation, I extended these methodologies into biomedical ontology development. First, I reviewed existing methodologies and systems developed in the fields of NLP, IR, and IE, and discussed how existing methods can benefit the development of biomedical ontologies. This previously unconducted review was published in the Journal of Biomedical Informatics. Second, I compared the effectiveness of three methods from two different approaches, the symbolic (the Hearst method) and the statistical (the Church and Lin methods), using clinical free-text documents. Third, I developed a methodological framework for Ontology Learning (OL) evaluation and comparison. This framework permits evaluation of the two types of OL approaches that include three OL methods. The significance of this work is as follows: 1) The results from the comparative study showed the potential of these methods for biomedical ontology enrichment. For the two targeted domains (NCIT and RadLex), the Hearst method revealed an average of 21% and 11% new concept acceptance rates, respectively. The Lin method produced a 74% acceptance rate for NCIT; the Church method, 53%. As a result of this study (published in the Journal of Methods of Information in Medicine), many suggested candidates have been incorporated into the NCIT; 2) The evaluation framework is flexible and general enough that it can analyze the performance of ontology enrichment methods for many domains, thus expediting the process of automation and minimizing the likelihood that key concepts and relationships would be missed as domain knowledge evolves

Automatic Pain Assessment by Learning from Multiple Biopotentials

Kivun täsmällinen arviointi on tärkeää kivunhallinnassa, erityisesti sairaan- hoitoa vaativille ipupotilaille. Kipu on subjektiivista, sillä se ei ole pelkästään aistituntemus, vaan siihen saattaa liittyä myös tunnekokemuksia. Tällöin itsearviointiin perustuvat kipuasteikot ovat tärkein työkalu, niin auan kun potilas pystyy kokemuksensa arvioimaan. Arviointi on kuitenkin haasteellista potilailla, jotka eivät itse pysty kertomaan kivustaan. Kliinisessä hoito- työssä kipua pyritään objektiivisesti arvioimaan esimerkiksi havainnoimalla fysiologisia muuttujia kuten sykettä ja käyttäytymistä esimerkiksi potilaan kasvonilmeiden perusteella. Tutkimuksen päätavoitteena on automatisoida arviointiprosessi hyödyntämällä koneoppimismenetelmiä yhdessä biosignaalien prosessointnin kanssa. Tavoitteen saavuttamiseksi mitattiin autonomista keskushermoston toimintaa kuvastavia biopotentiaaleja: sydänsähkökäyrää, galvaanista ihoreaktiota ja kasvolihasliikkeitä mittaavaa lihassähkökäyrää. Mittaukset tehtiin terveillä vapaaehtoisilla, joille aiheutettiin kokeellista kipuärsykettä. Järestelmän kehittämiseen tarvittavaa tietokantaa varten rakennettiin biopotentiaaleja keräävä Internet of Things -pohjainen tallennusjärjestelmä. Koostetun tietokannan avulla kehitettiin biosignaaleille prosessointimenetelmä jatku- vaan kivun arviointiin. Signaaleista eroteltiin piirteitä sekuntitasoon mukautetuilla aikaikkunoilla. Piirteet visualisoitiin ja tarkasteltiin eri luokittelijoilla kivun ja kiputason tunnistamiseksi. Parhailla luokittelumenetelmillä saavutettiin kivuntunnistukseen 90% herkkyyskyky (sensitivity) ja 84% erottelukyky (specificity) ja kivun voimakkuuden arviointiin 62,5% tarkkuus (accuracy). Tulokset vahvistavat kyseisen käsittelytavan käyttökelpoisuuden erityis- esti tunnistettaessa kipua yksittäisessä arviointi-ikkunassa. Tutkimus vahvistaa biopotentiaalien avulla kehitettävän automatisoidun kivun arvioinnin toteutettavuuden kokeellisella kivulla, rohkaisten etenemään todellisen kivun tutkimiseen samoilla menetelmillä. Menetelmää kehitettäessä suoritettiin lisäksi vertailua ja yhteenvetoa automaattiseen kivuntunnistukseen kehitettyjen eri tutkimusten välisistä samankaltaisuuksista ja eroista. Tarkastelussa löytyi signaalien eroavaisuuksien lisäksi tutkimusmuotojen aiheuttamaa eroa arviointitavoitteisiin, mikä hankaloitti tutkimusten vertailua. Lisäksi pohdit- tiin mitkä perinteisten prosessointitapojen osiot rajoittavat tai edistävät ennustekykyä ja miten, sekä tuoko optimointi läpimurtoa järjestelmän näkökulmasta.Accurate pain assessment plays an important role in proper pain management, especially among hospitalized people experience acute pain. Pain is subjective in nature which is not only a sensory feeling but could also combine affective factors. Therefore self-report pain scales are the main assessment tools as long as patients are able to self-report. However, it remains a challenge to assess the pain from the patients who cannot self-report. In clinical practice, physiological parameters like heart rate and pain behaviors including facial expressions are observed as empirical references to infer pain objectively. The main aim of this study is to automate such process by leveraging machine learning methods and biosignal processing. To achieve this goal, biopotentials reflecting autonomic nervous system activities including electrocardiogram and galvanic skin response, and facial expressions measured with facial electromyograms were recorded from healthy volunteers undergoing experimental pain stimulus. IoT-enabled biopotential acquisition systems were developed to build the database aiming at providing compact and wearable solutions. Using the database, a biosignal processing flow was developed for continuous pain estimation. Signal features were extracted with customized time window lengths and updated every second. The extracted features were visualized and fed into multiple classifiers trained to estimate the presence of pain and pain intensity separately. Among the tested classifiers, the best pain presence estimating sensitivity achieved was 90% (specificity 84%) and the best pain intensity estimation accuracy achieved was 62.5%. The results show the validity of the proposed processing flow, especially in pain presence estimation at window level. This study adds one more piece of evidence on the feasibility of developing an automatic pain assessment tool from biopotentials, thus providing the confidence to move forward to real pain cases. In addition to the method development, the similarities and differences between automatic pain assessment studies were compared and summarized. It was found that in addition to the diversity of signals, the estimation goals also differed as a result of different study designs which made cross dataset comparison challenging. We also tried to discuss which parts in the classical processing flow would limit or boost the prediction performance and whether optimization can bring a breakthrough from the system’s perspective

Automatic Population of Structured Reports from Narrative Pathology Reports

There are a number of advantages for the use of structured pathology reports: they can ensure the accuracy and completeness of pathology reporting; it is easier for the referring doctors to glean pertinent information from them. The goal of this thesis is to extract pertinent information from free-text pathology reports and automatically populate structured reports for cancer diseases and identify the commonalities and differences in processing principles to obtain maximum accuracy. Three pathology corpora were annotated with entities and relationships between the entities in this study, namely the melanoma corpus, the colorectal cancer corpus and the lymphoma corpus. A supervised machine-learning based-approach, utilising conditional random fields learners, was developed to recognise medical entities from the corpora. By feature engineering, the best feature configurations were attained, which boosted the F-scores significantly from 4.2% to 6.8% on the training sets. Without proper negation and uncertainty detection, the quality of the structured reports will be diminished. The negation and uncertainty detection modules were built to handle this problem. The modules obtained overall F-scores ranging from 76.6% to 91.0% on the test sets. A relation extraction system was presented to extract four relations from the lymphoma corpus. The system achieved very good performance on the training set, with 100% F-score obtained by the rule-based module and 97.2% F-score attained by the support vector machines classifier. Rule-based approaches were used to generate the structured outputs and populate them to predefined templates. The rule-based system attained over 97% F-scores on the training sets. A pipeline system was implemented with an assembly of all the components described above. It achieved promising results in the end-to-end evaluations, with 86.5%, 84.2% and 78.9% F-scores on the melanoma, colorectal cancer and lymphoma test sets respectively

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

Early diagnosis of disorders based on behavioural shifts and biomedical signals

There are many disorders that directly affect people’s behaviour. The people that are suffering from such a disorder are not aware of their situation, and too often the disorders are identified by relatives or co-workers because they notice behavioural shifts. However, when these changes become noticeable, it is often too late and irreversible damages have already been produced. Early detection is the key to prevent severe health-related damages and healthcare costs, as well as to improve people’s quality of life. Nowadays, in full swing of ubiquitous computing paradigm, users’ behaviour patterns can be unobtrusively monitored by means of interactions with many electronic devices. The application of this technology for the problem at hand would lead to the development of systems that are able to monitor disorders’ onset and progress in an ubiquitous and unobtrusive way, thus enabling their early detection. Some attempts for the detection of specific disorders based on these technologies have been proposed, but a global methodology that could be useful for the early detection of a wide range of disorders is still missing. This thesis aims to fill that gap by presenting as main contribution a global screening methodology for the early detection of disorders based on unobtrusive monitoring of physiological and behavioural data. The proposed methodology is the result of a cross-case analysis between two individual validation scenarios: stress in the workplace and Alzheimer’s Disease (AD) at home, from which conclusions that contribute to each of the two research fields have been drawn. The analysis of similarities and differences between the two case studies has led to a complete and generalized definition of the steps to be taken for the detection of a new disorder based on ubiquitous computing.Jendearen portaeran eragin zuzena duten gaixotasun ugari daude. Hala ere, askotan, gaixotasuna pairatzen duten pertsonak ez dira euren egoerataz ohartzen, eta familiarteko edo lankideek identifikatu ohi dute berau jokabide aldaketetaz ohartzean. Portaera aldaketa hauek nabarmentzean, ordea, beranduegi izan ohi da eta atzerazeinak diren kalteak eraginda egon ohi dira. Osasun kalte larriak eta gehiegizko kostuak ekiditeko eta gaixoen bizi kalitatea hobetzeko gakoa, gaixotasuna garaiz detektatzea da. Gaur egun, etengabe zabaltzen ari den Nonahiko Konputazioaren paradigmari esker, erabiltzaileen portaera ereduak era diskretu batean monitorizatu daitezke, gailu teknologikoekin izandako interakzioari esker. Eskuartean dugun arazoari konponbidea emateko teknologi hau erabiltzeak gaixotasunen sorrera eta aurrerapena nonahi eta era diskretu batean monitorizatzeko gai diren sistemak garatzea ekarriko luke, hauek garaiz hautematea ahalbidetuz. Gaixotasun konkretu batzuentzat soluzioak proposatu izan dira teknologi honetan oinarrituz, baina metodologia orokor bat, gaixotasun sorta zabal baten detekzio goiztiarrerako erabilgarria izango dena, oraindik ez da aurkeztu. Tesi honek hutsune hori betetzea du helburu, mota honetako gaixotasunak garaiz hautemateko, era diskretu batean atzitutako datu fisiologiko eta konportamentalen erabileran oinarritzen den behaketa sistema orokor bat proposatuz. Proposatutako metodologia bi balidazio egoera desberdinen arteko analisi gurutzatu baten emaitza da: estresa lantokian eta Alzheimerra etxean, balidazio egoera bakoitzari dagozkion ekarpenak ere ondorioztatu ahal izan direlarik. Bi kasuen arteko antzekotasun eta desberdintasunen analisiak, gaixotasun berri bat nonahiko konputazioan oinarrituta detektatzeko jarraitu beharreko pausoak bere osotasunean eta era orokor batean definitzea ahalbidetu du

Current approaches in managing food allergy in Australian settings

Michael Sheridan analysed undeclared food allergens in products for sale at Asian retail stores in Melbourne, finding a large proportion of undeclared allergens and non-compliant labelling, resulting in recommendations and consultation with Government agencies. A food recall notification app tool with accompanying website, was developed, and app downloads were found to increase with media attention