237 research outputs found

    Physiological complexity of EEG as a proxy for dementia risk prediction: a review and preliminary cross-section analysis

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    The aim of this work is to give the readers a review (perspective) of prior work on this kind of complexity-based detection from resting-state EEG and present our preliminary cross-section analysis results on how EEG complexity of supposedly healthy senior persons can serve as an early warning to clinicians. Together with the use of wearables for health, this approach to early detection can be done out of clinical setting improving the chances of increasing the quality of life in seniors.Comment: 19 pages, 1 figure, 1 tabl

    Degradation of EEG microstates patterns in subjective cognitive decline and mild cognitive impairment: Early biomarkers along the Alzheimer's Disease continuum?

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    Alzheimer's disease (AD) pathological changes may begin up to decades earlier than the appearance of the first symptoms of cognitive decline. Subjective cognitive decline (SCD) could be the first pre-clinical sign of possible AD, which might be followed by mild cognitive impairment (MCI), the initial stage of clinical cognitive decline. However, the neural correlates of these prodromic stages are not completely clear yet. Recent studies suggest that EEG analysis tools characterizing the cortical activity as a whole, such as microstates and cortical regions connectivity, might support a characterization of SCD and MCI conditions. Here we test this approach by performing a broad set of analyses to identify the prominent EEG markers differentiating SCD (n = 57), MCI (n = 46) and healthy control subjects (HC, n = 19). We found that the salient differences were in the temporal structure of the microstates patterns, with MCI being associated with less complex sequences due to the altered transition probability, frequency and duration of canonic microstate C. Spectral content of EEG, network connectivity, and spatial arrangement of microstates were instead largely similar in the three groups. Interestingly, comparing properties of EEG microstates in different cerebrospinal fluid (CSF) biomarkers profiles, we found that canonic microstate C displayed significant differences in topography in AD-like profile. These results show that the progression of dementia might be associated with a degradation of the cortical organization captured by microstates analysis, and that this leads to altered transitions between cortical states. Overall, our approach paves the way for the use of non-invasive EEG recordings in the identification of possible biomarkers of progression to AD from its prodromal states

    Space, time and motion in a multisensory world

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    When interacting with environmental events, humans acquire information from different senses and combine these inputs within a coherent representation of the world. The present doctoral thesis aims at investigating how humans represent space, time, and motion through auditory and visual sensory modalities. It has been widely demonstrated a predisposition of different sensory systems towards the processing of different domains of representation, with hearing that prevails in representing the time domain and vision that is the most reliable sense for processing the space domain. Given this strong link between sensory modality and domain of representation, one objective of this thesis is to deepen the knowledge of the neural organization of multisensory spatial and temporal skills in healthy adults. In addition, by using blindness as a model to unravel the role of vision in the development of spatio-temporal abilities, this thesis explores the interaction of the spatial and temporal domains in the acoustic motion perception of early blind individuals. The interplay between space and time has also been explained as the result of humans performing actions in the surrounding environment since to carry out goal-directed motor behaviors it is useful for a person to associate the spatial and temporal information of one’s target into a shared mental map. In this regard, the present project also questions how the brain processes spatio-temporal cues of external events when it comes to manually intercepting moving objects with one hand. Finally, in light of the above results, this dissertation incorporates the development of a novel portable device, named MultiTab, for the behavioral evaluation of the processing of space, time, and motor responses, through the visual and acoustic sensory modality. For the purposes of this thesis, four methodological approaches have been employed: i) electroencephalogram (EEG) technique, to explore the cortical activation associated with multisensory spatial and temporal tasks; ii) psychophysical methods, to measure the relationship between stimuli in motion and the acoustic speed perception of blind and sighted individuals; iii) motion capture techniques, to measure indices of movements during an object’s interception task; iv) design and technical-behavioral validation of a new portable device. Studies of the present dissertation indicate the following results. First, this thesis highlights an early cortical gain modulation of sensory areas that depends on the domain of representation to process, with auditory areas mainly involved in the multisensory processing of temporal inputs, and visual areas of spatial inputs. Moreover, for the spatial domain specifically, the neural modulation of visual areas is also influenced by the kind of spatial layout representing multisensory stimuli. Second, this project shows that lack of vision influences the ability to process the speed of moving sounds by altering how blind individuals make use of the sounds’ temporal features. This result suggests that visual experience in the first years of life is a crucial factor when dealing with combined spatio-temporal information. Third, data of this thesis demonstrate that typically developing individuals manually intercepting a moving object with one hand take into consideration the item’s spatio-temporal cues, by adjusting their interceptive movements according to the object’s speed. Finally, the design and validation of MultiTab show its utility in the evaluation of multisensory processing such as the manual localization of audiovisual spatialized stimuli. Overall, findings from this thesis contribute to a more in-depth picture of how the human brain represents space, time, and motion through different senses. Moreover, they provide promising implications in exploring novel technological methods for the assessment and training of these dimensions in typical and atypical populations

    Towards naturalistic scanning environments for wearable magnetoencephalography

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    Magnetoencephalography (MEG) is a neuroimaging technique that probes human brain function, by measuring the magnetic fields generated at the scalp by current flow in assemblies of neurons. A direct measure of neural activity, MEG offers high spatiotemporal resolution, but limitations imposed by superconducting sensor technologies impede its clinical utility. Specifically, neuromagnetic fields are up to a billion times smaller than that of the Earth, meaning MEG must be performed inside a magnetically shielded room (MSR), which is typically expensive, heavy, and difficult to site. Furthermore, current MEG systems employ superconducting quantum interference devices (SQUIDs) to detect these tiny magnetic fields, however, these sensors require cryogenic cooling with liquid helium. Consequently, scanners are bulky, expensive, and the SQUIDs must be arranged in a fixed, one-size-fits-all array. Any movement relative to the fixed sensors impacts data quality, meaning participant movement in MEG is severely restricted. The development of technology to enable a wearable MEG system allowing free participant movement would generate a step change for the field. Optically-pumped magnetometers (OPMs) are an alternative magnetic field detector recently developed with sufficient sensitivity for MEG measurements. Operating at body temperature, in a small and lightweight sensor package, OPMs offer the potential for a wearable MEG scanner that allows participant movement, with sensors mounted on the scalp in a helmet or cap. However, OPMs operate around a zero-field resonance, resulting in a narrow dynamic range that may be easily exceeded by movement of the sensor within a background magnetic field. Enabling a full range of participant motion during an OPM-MEG scan therefore presents a significant challenge, requiring precise control of the background magnetic field. This thesis describes the development of techniques to better control the magnetic environment for OPM-MEG. This includes greater reduction of background magnetic fields over a fixed region to minimise motion artefacts and facilitate larger movements, and the application of novel, multi-coil active magnetic shielding systems to enable flexibility in participant positioning within the MSR. We outline a new approach to map background magnetic fields more accurately, reducing the remnant magnetic field to <300 pT and yielding a five-fold reduction in motion artefact, to allow detection of a visual steady-state evoked response during continuous head motion. Employing state-of-the-art, triaxial OPMs alongside this precision magnetic field control technique, we map motor function during a handwriting task involving naturalistic head movements and investigate the advantages of triaxial sensitivity for MEG data analysis. Using multi-coil active magnetic shielding, we map motor function consistently in the same participant when seated and standing, and demonstrate the first OPM-MEG hyperscanning experiments. Finally, we outline how the integration of a multi-coil system into the walls of a lightweight MSR, when coupled with field control over a larger volume, provides an open scanning environment. In sum, these developments represent a significant step towards realising the full potential of OPM-MEG as a wearable functional neuroimaging technology

    Modulating consciousness with acoustic-electric stimulation

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    An Electroencephalographic Investigation of the Encoding of Sound Source Elevation in the Human Cortex

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    Sound localization is of great ecological importance because it provides spa- tial perception outside the visual field. However, unlike other sensory systems, the auditory system does not represent the location of a stimulus on the level of the sensory epithelium in the cochlea. Instead, the position of a sound source has to be computed based on different localization cues. Different cues are informative of a sound sources azimuth and elevation, which, when taken together, describe the sources location in a polar coordinate system. There is a body of knowledge regarding the acoustical cues and the neural circuits in the brainstem required to perceive sound source azimuth and elevation. However, our understanding of the encoding of sound source location on the level of the cortex is lacking especially what concerns elevation. Within the scope of this thesis, we established an experimental setup to study auditory spatial perception while recording the listeners brain activity using electroencephalography. We conducted two experiments on the encoding of sound source elevation in the human cortex. Both experiments results are compatible with the hypothesis that the cortex represents sound source elevation in a population rate code where the response amplitude decreases linearly with increasing elevation. Decoding of the recorded brain activity revealed that a distinct neural representation of differently elevated sound sources was predictive of behavioral performance. An exploratory analysis indicated an increase in the amplitude of oscillations in visual areas when the subject localized sounds during eccentric eye positions. More research in this direction could help shed light on the interactions between the visual and auditory systems regarding spatial perception. The experiments presented in this dissertation are, to our knowledge, the first studies that demonstrate the encoding of sound source elevation in the human cortex by using a direct measure of neural activity (i.e., electroencephalography).:Abstract . . . . . . . . . . . . . . . . . . . . . . 1 Zusammenfassung . . . . . . . . . . . . . . . . . . . . . . 7 1 Electroencephalography 13 1.1 Event Related Potentials and Oscillations . . . . . . . . . . . . 13 1.2 Comparison to other Methods . . . . . . . . . . . . . . . . . . . 14 1.3 EEG Apparatus . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 1.4 Preprocessing . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 1.4.1 Filtering . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 1.4.2 Referencing . . . . . . . . . . . . . . . . . . . . . . . . . 19 1.4.3 Eye Blinks . . . . . . . . . . . . . . . . . . . . . . . . . . 22 1.4.4 Epoch Rejection . . . . . . . . . . . . . . . . . . . . . . . 22 1.4.5 Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . 24 1.5 Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 1.5.1 Decoding . . . . . . . . . . . . . . . . . . . . . . . . . . 25 1.5.2 Nonparametric Permutation Testing . . . . . . . . . . . 26 1.5.3 Source Separation . . . . . . . . . . . . . . . . . . . . . . 28 2 Sound Localization in the Brain . . . . . . . . . . . . . . . . . . . . 31 2.1 The Spatial Perception of Sound . . . . . . . . . . . . . . . . . . 32 2.1.1 Interaural Cues . . . . . . . . . . . . . . . . . . . . . . . 32 2.1.2 Spectral Cues . . . . . . . . . . . . . . . . . . . . . . . . 33 2.2 Brain Mechanisms for Sound Localization . . . . . . . . . . . . 37 2.2.1 Auditory Pathway . . . . . . . . . . . . . . . . . . . . . 38 2.2.2 Extracting Localization Cues . . . . . . . . . . . . . . . 40 2.2.3 Neural Representation of Auditory Space . . . . . . . . 42 2.2.4 The Dual Pathway Model . . . . . . . . . . . . . . . . . 45 2.2.5 A Dominant Hemisphere for Sound Localization? . . . 47 2.3 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 3 A Free Field Setup for Psychoacoustics 51 3.1 Design of the Experimental Setup . . . . . . . . . . . . . . . . . 51 3.1.1 Loudspeakers . . . . . . . . . . . . . . . . . . . . . . . . 54 3.1.2 Processors . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.1.3 Cameras . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.1.4 Coordinate Systems . . . . . . . . . . . . . . . . . . . . 56 3.2 Operating the Setup . . . . . . . . . . . . . . . . . . . . . . . . . 57 3.2.1 Workflow . . . . . . . . . . . . . . . . . . . . . . . . . . 58 3.2.2 Loudspeaker Equalization . . . . . . . . . . . . . . . . . 59 3.3 Head Pose Estimation . . . . . . . . . . . . . . . . . . . . . . . 61 3.3.1 Landmark Detection . . . . . . . . . . . . . . . . . . . . 62 3.3.2 Perspective-n-Point Problem . . . . . . . . . . . . . . . 62 3.3.3 Camera-to-World Conversion . . . . . . . . . . . . . . . 63 3.4 A Toolbox for Psychoacoustics . . . . . . . . . . . . . . . . . . 64 4 A Linear Population Rate Code for Elevation 67 4.1 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 4.1.1 Participants . . . . . . . . . . . . . . . . . . . . . . . . . 68 4.1.2 Experimental Protocol . . . . . . . . . . . . . . . . . . . 69 4.2 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 4.2.1 Behavioral Performance . . . . . . . . . . . . . . . . . . 70 4.2.2 ERP Components . . . . . . . . . . . . . . . . . . . . . . 70 4.2.3 Elevation Encoding . . . . . . . . . . . . . . . . . . . . . 72 4.2.4 Effect of Eye-Position . . . . . . . . . . . . . . . . . . . . 74 4.3 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 5 Decoding of Brain Responses Predicts Localization Accuracy . . . 81 5.1 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 5.1.1 Participants . . . . . . . . . . . . . . . . . . . . . . . . . 82 5.1.2 Experimental Protocol . . . . . . . . . . . . . . . . . . . 82 5.2 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 5.2.1 Behavioral Performance . . . . . . . . . . . . . . . . . . 83 5.2.2 ERP Components . . . . . . . . . . . . . . . . . . . . . . 84 5.2.3 Decoding Brain Activity . . . . . . . . . . . . . . . . . . 86 5.2.4 Topography of Elevation Encoding . . . . . . . . . . . . 88 5.2.5 Elevation Tuning . . . . . . . . . . . . . . . . . . . . . . 89 5.2.6 Hemispheric Lateralization . . . . . . . . . . . . . . . . 91 5.3 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 A Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 B Publication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

    Earables: Wearable Computing on the Ears

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    Kopfhörer haben sich bei Verbrauchern durchgesetzt, da sie private AudiokanĂ€le anbieten, zum Beispiel zum Hören von Musik, zum Anschauen der neuesten Filme wĂ€hrend dem Pendeln oder zum freihĂ€ndigen Telefonieren. Dank diesem eindeutigen primĂ€ren Einsatzzweck haben sich Kopfhörer im Vergleich zu anderen Wearables, wie zum Beispiel Smartglasses, bereits stĂ€rker durchgesetzt. In den letzten Jahren hat sich eine neue Klasse von Wearables herausgebildet, die als "Earables" bezeichnet werden. Diese GerĂ€te sind so konzipiert, dass sie in oder um die Ohren getragen werden können. Sie enthalten verschiedene Sensoren, um die FunktionalitĂ€t von Kopfhörern zu erweitern. Die rĂ€umliche NĂ€he von Earables zu wichtigen anatomischen Strukturen des menschlichen Körpers bietet eine ausgezeichnete Plattform fĂŒr die Erfassung einer Vielzahl von Eigenschaften, Prozessen und AktivitĂ€ten. Auch wenn im Bereich der Earables-Forschung bereits einige Fortschritte erzielt wurden, wird deren Potenzial aktuell nicht vollstĂ€ndig abgeschöpft. Ziel dieser Dissertation ist es daher, neue Einblicke in die Möglichkeiten von Earables zu geben, indem fortschrittliche SensorikansĂ€tze erforscht werden, welche die Erkennung von bisher unzugĂ€nglichen PhĂ€nomenen ermöglichen. Durch die EinfĂŒhrung von neuartiger Hardware und Algorithmik zielt diese Dissertation darauf ab, die Grenzen des Erreichbaren im Bereich Earables zu verschieben und diese letztlich als vielseitige Sensorplattform zur Erweiterung menschlicher FĂ€higkeiten zu etablieren. Um eine fundierte Grundlage fĂŒr die Dissertation zu schaffen, synthetisiert die vorliegende Arbeit den Stand der Technik im Bereich der ohr-basierten Sensorik und stellt eine einzigartig umfassende Taxonomie auf der Basis von 271 relevanten Publikationen vor. Durch die Verbindung von Low-Level-Sensor-Prinzipien mit Higher-Level-PhĂ€nomenen werden in der Dissertation anschließ-end Arbeiten aus verschiedenen Bereichen zusammengefasst, darunter (i) physiologische Überwachung und Gesundheit, (ii) Bewegung und AktivitĂ€t, (iii) Interaktion und (iv) Authentifizierung und Identifizierung. Diese Dissertation baut auf der bestehenden Forschung im Bereich der physiologischen Überwachung und Gesundheit mit Hilfe von Earables auf und stellt fortschrittliche Algorithmen, statistische Auswertungen und empirische Studien vor, um die Machbarkeit der Messung der Atemfrequenz und der Erkennung von Episoden erhöhter Hustenfrequenz durch den Einsatz von In-Ear-Beschleunigungsmessern und Gyroskopen zu demonstrieren. Diese neuartigen Sensorfunktionen unterstreichen das Potenzial von Earables, einen gesĂŒnderen Lebensstil zu fördern und eine proaktive Gesundheitsversorgung zu ermöglichen. DarĂŒber hinaus wird in dieser Dissertation ein innovativer Eye-Tracking-Ansatz namens "earEOG" vorgestellt, welcher AktivitĂ€tserkennung erleichtern soll. Durch die systematische Auswertung von Elektrodenpotentialen, die um die Ohren herum mittels eines modifizierten Kopfhörers gemessen werden, eröffnet diese Dissertation einen neuen Weg zur Messung der Blickrichtung. Dabei ist das Verfahren weniger aufdringlich und komfortabler als bisherige AnsĂ€tze. DarĂŒber hinaus wird ein Regressionsmodell eingefĂŒhrt, um absolute Änderungen des Blickwinkels auf der Grundlage von earEOG vorherzusagen. Diese Entwicklung eröffnet neue Möglichkeiten fĂŒr Forschung, welche sich nahtlos in das tĂ€gliche Leben integrieren lĂ€sst und tiefere Einblicke in das menschliche Verhalten ermöglicht. Weiterhin zeigt diese Arbeit, wie sich die einzigarte Bauform von Earables mit Sensorik kombinieren lĂ€sst, um neuartige PhĂ€nomene zu erkennen. Um die Interaktionsmöglichkeiten von Earables zu verbessern, wird in dieser Dissertation eine diskrete Eingabetechnik namens "EarRumble" vorgestellt, die auf der freiwilligen Kontrolle des Tensor Tympani Muskels im Mittelohr beruht. Die Dissertation bietet Einblicke in die Verbreitung, die Benutzerfreundlichkeit und den Komfort von EarRumble, zusammen mit praktischen Anwendungen in zwei realen Szenarien. Der EarRumble-Ansatz erweitert das Ohr von einem rein rezeptiven Organ zu einem Organ, das nicht nur Signale empfangen, sondern auch Ausgangssignale erzeugen kann. Im Wesentlichen wird das Ohr als zusĂ€tzliches interaktives Medium eingesetzt, welches eine freihĂ€ndige und augenfreie Kommunikation zwischen Mensch und Maschine ermöglicht. EarRumble stellt eine Interaktionstechnik vor, die von den Nutzern als "magisch und fast telepathisch" beschrieben wird, und zeigt ein erhebliches ungenutztes Potenzial im Bereich der Earables auf. Aufbauend auf den vorhergehenden Ergebnissen der verschiedenen Anwendungsbereiche und Forschungserkenntnisse mĂŒndet die Dissertation in einer offenen Hard- und Software-Plattform fĂŒr Earables namens "OpenEarable". OpenEarable umfasst eine Reihe fortschrittlicher Sensorfunktionen, die fĂŒr verschiedene ohrbasierte Forschungsanwendungen geeignet sind, und ist gleichzeitig einfach herzustellen. Hierdurch werden die EinstiegshĂŒrden in die ohrbasierte Sensorforschung gesenkt und OpenEarable trĂ€gt somit dazu bei, das gesamte Potenzial von Earables auszuschöpfen. DarĂŒber hinaus trĂ€gt die Dissertation grundlegenden Designrichtlinien und Referenzarchitekturen fĂŒr Earables bei. Durch diese Forschung schließt die Dissertation die LĂŒcke zwischen der Grundlagenforschung zu ohrbasierten Sensoren und deren praktischem Einsatz in realen Szenarien. Zusammenfassend liefert die Dissertation neue Nutzungsszenarien, Algorithmen, Hardware-Prototypen, statistische Auswertungen, empirische Studien und Designrichtlinien, um das Feld des Earable Computing voranzutreiben. DarĂŒber hinaus erweitert diese Dissertation den traditionellen Anwendungsbereich von Kopfhörern, indem sie die auf Audio fokussierten GerĂ€te zu einer Plattform erweitert, welche eine Vielzahl fortschrittlicher SensorfĂ€higkeiten bietet, um Eigenschaften, Prozesse und AktivitĂ€ten zu erfassen. Diese Neuausrichtung ermöglicht es Earables sich als bedeutende Wearable Kategorie zu etablieren, und die Vision von Earables als eine vielseitige Sensorenplattform zur Erweiterung der menschlichen FĂ€higkeiten wird somit zunehmend realer

    Differential Models, Numerical Simulations and Applications

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    This Special Issue includes 12 high-quality articles containing original research findings in the fields of differential and integro-differential models, numerical methods and efficient algorithms for parameter estimation in inverse problems, with applications to biology, biomedicine, land degradation, traffic flows problems, and manufacturing systems

    Cognitive and Neurophysiological Models of Brain Asymmetry

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    Asymmetry is an inherent characteristic of brain organization in both humans and other vertebrate species, and is evident at the behavioral, neurophysiological, and structural levels. Brain asymmetry underlies the organization of several cognitive systems, such as emotion, communication, and spatial processing. Despite this ubiquity of asymmetries in the vertebrate brain, we are only beginning to understand the complex neuronal mechanisms underlying the interaction between hemispheric asymmetries and cognitive systems. Unfortunately, despite the vast number of empirical studies on brain asymmetries, theoretical models that aim to provide mechanistic explanations of hemispheric asymmetries are sparse in the field. Therefore, this Special Issue aims to highlight empirically based mechanistic models of brain asymmetry. Overall, six theoretical and four empirical articles were published in the Special Issue, covering a wide range of topics, from human handedness to auditory laterality in bats. Two key challenges for theoretical models of brain asymmetry are the integration of increasingly complex molecular data into testable models, and the creation of theoretical models that are robust and testable across different species

    Prediction and causal inference in the transition from acute to chronic low back pain

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    The overarching aim of this thesis was to enhance our understanding of the neurobiological risk factors associated with the transition from acute to chronic Low back pain (LBP). To achieve this aim, the Understanding persistent Pain Where it ResiDes (UPWaRD) study was conducted. In this thesis, six chapters describe the background, methods, and results of the UPWaRD study. Chapter 2 describes the protocol, published ‘a priori’ for developing a multivariable prediction model, including candidate predictors selected from the neurobiological (e.g. sensorimotor cortical excitability assessed by sensory and motor evoked potentials, Brain Derived Neurotrophic Factor [BDNF] genotype), psychological (e.g. depression and anxiety), symptom-related (e.g. LBP history) and demographic domains. Chapter 3 builds on the study protocol in the form of a cohort profile, describing baseline characteristics of 120 people experiencing an acute LBP episode and 57 pain-free control participants that form the UPWaRD cohort. Chapter 4 reports the results of the multivariable prediction model developed in 120 people experiencing acute LBP. To further understand the importance of these prognostic factors we developed a causal model of chronic LBP using directed acyclic graphs. The methodology and statistical analysis plan for drawing causal inferences, thus transparently reporting our causal assumptions, are reported in Chapter 5. Chapter 6 then provides the first evidence that low sensory cortex excitability during an acute LBP episode is a causal mechanism underpinning the development of chronic LBP. Finally, in Chapter 7, we report the results of a proteomic analysis, using hydrophobic interaction chromatography and electrospray ionization tandem mass spectrometry. Taken together this thesis makes an extensive and original contribution to our understanding of neurobiological risk factors involved in the transition from acute to chronic LBP. Not only is the inclusion of neurobiological prognostic factors in multivariable clinical prediction models a promising direction for future research that aims to identify people at high risk of poor outcome, but low sensory cortex excitability during acute LBP may be a promising causal mechanism that future treatments could target during acute LBP in the hope of expediting recovery and preventing the development of chronic LBP. Further, this thesis provides some of the earliest evidence to suggest sex-specific differential expression of proteins, measured from human serum, contributes to recovery status at three-month follow-up. This work provides foundational evidence for future research exploring strategies targeting distinct immune system processes in males and females that may interfere with the transition from acute to chronic LBP
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