2,792 research outputs found
On the interplay between speech perception and production: insights from research and theories
The study of spoken communication has long been entrenched in a debate surrounding the interdependence of speech production and perception. This mini review summarizes findings from prior studies to elucidate the reciprocal relationships between speech production and perception. We also discuss key theoretical perspectives relevant to speech perception-production loop, including hyper-articulation and hypo-articulation (H&H) theory, speech motor theory, direct realism theory, articulatory phonology, the Directions into Velocities of Articulators (DIVA) and Gradient Order DIVA (GODIVA) models, and predictive coding. Building on prior findings, we propose a revised auditory-motor integration model of speech and provide insights for future research in speech perception and production, focusing on the effects of impaired peripheral auditory systems
Neuroimaging investigations of cortical specialisation for different types of semantic knowledge
Embodied theories proposed that semantic knowledge is grounded in motor and perceptual experiences. This leads to two questions: (1) whether the neural underpinnings of perception are also necessary for semantic cognition; (2) how do biases towards different sensorimotor experiences cause brain regions to specialise for particular types of semantic information. This thesis tackles these questions in a series of neuroimaging and behavioural investigations.
Regarding question 1, strong embodiment theory holds that semantic representation is reenactment of corresponding experiences, and brain regions for perception are necessary for comprehending modality-specific concepts. However, the weak embodiment view argues that reenactment may not be necessary, and areas near to perceiving regions may be sufficient to support semantic representation.
In the particular case of motion concepts, lateral occipital temporal cortex (LOTC) has been long identified as an important area, but the roles of its different subregions are still uncertain. Chapter 3 examined how different parts of LOTC reacted to written descriptions of motion and static events, using multiple analysis methods. A series of anterior to posterior sub-regions were analyzed through univariate, multivariate pattern analysis (MVPA), and psychophysical interaction (PPI) analyses. MVPA revealed strongest decoding effects for motion vs. static events in the posterior parts of LOTC, including both visual motion area (V5) and posterior middle temporal gyrus (pMTG). In contrast, only the middle portion of LOTC showed increased activation for motion sentences in univariate analyses. PPI analyses showed increased functional connectivity between posterior LOTC and the multiple demand network for motion events. These findings suggest that posterior LOTC, which overlapped with the motion perception V5 region, is selectively involved in comprehending motion events, while the anterior part of LOTC contributes to general semantic processing.
Regarding question 2, the hub-and-spoke theory suggests that anterior temporal lobe (ATL) acts as a hub, using inputs from modality-specific regions to construct multimodal concepts. However, some researchers propose temporal parietal cortex (TPC) as an additional hub, specialised in processing and integrating interaction and contextual information (e.g., for actions and locations). These hypotheses are summarized as the "dual-hub theory" and different aspects of this theory were investigated in in Chapters 4 and 5.
Chapter 4 focuses on taxonomic and thematic relations. Taxonomic relations (or categorical relations) occur when two concepts belong to the same category (e.g., ‘dog’ and ‘wolf’ are both canines). In contrast, thematic relations (or associative relations) refer to situations that two concepts co-occur in events or scenes (e.g., ‘dog’ and ‘bone’), focusing on the interaction or association between concepts. Some studies have indicated ATL specialization for taxonomic relations and TPC specialization for thematic relations, but others have reported inconsistent or even converse results. Thus Chapter 4 first conducted an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies contrasting taxonomic and thematic relations. This found that thematic relations reliably engage action and location processing regions (left pMTG and SMG), while taxonomic relations only showed consistent effects in the right occipital lobe. A primed semantic judgement task was then used to test the dual-hub theory’s prediction that taxonomic relations are heavily reliant on colour and shape knowledge, while thematic relations rely on action and location knowledge. This behavioural experiment revealed that action or location priming facilitated thematic relation processing, but colour and shape did not lead to priming effects for taxonomic relations. This indicates that thematic relations rely more on action and location knowledge, which may explain why the preferentially engage TPC, whereas taxonomic relations are not specifically linked to shape and colour features. This may explain why they did not preferentially engage left ATL.
Chapter 5 concentrates on event and object concepts. Previous studies suggest ATL specialization for coding similarity of objects’ semantics, and angular gyrus (AG) specialization for sentence and event structure representation. In addition, in neuroimaging studies, event semantics are usually investigated using complex temporally extended stimuli, unlike than the single-concept stimuli used to investigate object semantics. Thus chapter 5 used representational similarity analysis (RSA), univariate analysis, and PPI analysis to explore neural activation patterns for event and object concepts presented as static images. Bilateral AGs encoded semantic similarity for event concepts, with the left AG also coding object similarity. Bilateral ATLs encoded semantic similarity for object concepts but also for events. Left ATL exhibited stronger coding for events than objects. PPI analysis revealed stronger connections between left ATL and right pMTG, and between right AG and bilateral inferior temporal gyrus (ITG) and middle occipital gyrus, for event concepts compared to object concepts. Consistent with the meta-analysis in chapter 4, the results in chapter 5 support the idea of partial specialization in AG for event semantics but do not support ATL specialization for object semantics. In fact, both the meta-analysis and chapter 5 findings suggest greater ATL involvement in coding objects' associations compared to their similarity.
To conclude, the thesis provides support for the idea that perceptual brain regions are engaged in conceptual processing, in the case of motion concepts. It also provides evidence for a specialised role for TPC regions in processing thematic relations (pMTG) and event concepts (AG). There was mixed evidence for specialisation within the ATLs and this remains an important target for future research
On the Utility of Representation Learning Algorithms for Myoelectric Interfacing
Electrical activity produced by muscles during voluntary movement is a reflection of the firing patterns of relevant motor neurons and, by extension, the latent motor intent driving the movement. Once transduced via electromyography (EMG) and converted into digital form, this activity can be processed to provide an estimate of the original motor intent and is as such a feasible basis for non-invasive efferent neural interfacing. EMG-based motor intent decoding has so far received the most attention in the field of upper-limb prosthetics, where alternative means of interfacing are scarce and the utility of better control apparent. Whereas myoelectric prostheses have been available since the 1960s, available EMG control interfaces still lag behind the mechanical capabilities of the artificial limbs they are intended to steer—a gap at least partially due to limitations in current methods for translating EMG into appropriate motion commands. As the relationship between EMG signals and concurrent effector kinematics is highly non-linear and apparently stochastic, finding ways to accurately extract and combine relevant information from across electrode sites is still an active area of inquiry.This dissertation comprises an introduction and eight papers that explore issues afflicting the status quo of myoelectric decoding and possible solutions, all related through their use of learning algorithms and deep Artificial Neural Network (ANN) models. Paper I presents a Convolutional Neural Network (CNN) for multi-label movement decoding of high-density surface EMG (HD-sEMG) signals. Inspired by the successful use of CNNs in Paper I and the work of others, Paper II presents a method for automatic design of CNN architectures for use in myocontrol. Paper III introduces an ANN architecture with an appertaining training framework from which simultaneous and proportional control emerges. Paper Iv introduce a dataset of HD-sEMG signals for use with learning algorithms. Paper v applies a Recurrent Neural Network (RNN) model to decode finger forces from intramuscular EMG. Paper vI introduces a Transformer model for myoelectric interfacing that do not need additional training data to function with previously unseen users. Paper vII compares the performance of a Long Short-Term Memory (LSTM) network to that of classical pattern recognition algorithms. Lastly, paper vIII describes a framework for synthesizing EMG from multi-articulate gestures intended to reduce training burden
Ovarian hormones shape brain structure, function, and chemistry: A neuropsychiatric framework for female brain health
There are robust sex differences in brain anatomy, function, as well as neuropsychiatric and neurodegenerative disease risk (1-6), with women approximately twice as likely to suffer from a depressive illness as well as Alzheimer’s Disease. Disruptions in ovarian hormones likely play a role in such disproportionate disease prevalence, given that ovarian hormones serve as key regulators of brain functional and structural plasticity and undergo major fluctuations across the female lifespan (7-9). From a clinical perspective, there is a wellreported increase in depression susceptibility and initial evidence for cognitive impairment or decline during hormonal transition states, such as the postpartum period and perimenopause (9-14). What remains unknown, however, is the underlying mechanism of how fluctuations in ovarian hormones interact with other biological factors to influence brain structure, function, and chemistry. While this line of research has translational relevance for over half the population, neuroscience is notably guilty of female participant exclusion in research studies, with the male brain implicitly treated as the default model and only a minority of basic and clinical neuroscience studies including a female sample (15-18). Female underrepresentation in neuroscience directly limits opportunities for basic scientific discovery; and without basic knowledge of the biological underpinnings of sex differences, we cannot address critical sexdriven differences in pathology. Thus, my doctoral thesis aims to deliberately investigate the influence of sex and ovarian hormones on brain states in health as well as in vulnerability to depression and cognitive impairment:Table of Contents
List of Abbreviations ..................................................................................................................... i
List of Figures .............................................................................................................................. ii
Acknowledgements .....................................................................................................................iii
1 INTRODUCTION .....................................................................................................................1
1.1 Lifespan approach: Sex, hormones, and metabolic risk factors for cognitive health .......3
1.2 Reproductive years: Healthy models of ovarian hormones, serotonin, and the brain ......4
1.2.1 Ovarian hormones and brain structure across the menstrual cycle ........................4
1.2.2 Serotonergic modulation and brain function in oral contraceptive users .................6
1.3 Neuropsychiatric risk models: Reproductive subtypes of depression ...............................8
1.3.1 Hormonal transition states and brain chemistry measured by PET imaging ...........8
1.3.2 Serotonin transporter binding across the menstrual cycle in PMDD patients .......10
2 PUBLICATIONS ....................................................................................................................12
2.1 Publication 1: Association of estradiol and visceral fat with structural brain networks
and memory performance in adults .................................................................................13
2.2 Publication 2: Longitudinal 7T MRI reveals volumetric changes in subregions of
human medial temporal lobe to sex hormone fluctuations ..............................................28
2.3 Publication 3: One-week escitalopram intake alters the excitation-inhibition balance
in the healthy female brain ...............................................................................................51
2.4 Publication 4: Using positron emission tomography to investigate hormone-mediated
neurochemical changes across the female lifespan: implications for depression ..........65
2.5 Publication 5: Increase in serotonin transporter binding across the menstrual cycle in
patients with premenstrual dysphoric disorder: a case-control longitudinal neuro-
receptor ligand PET imaging study ..................................................................................82
3 SUMMARY ...........................................................................................................................100
References ..............................................................................................................................107
Supplementary Publications ...................................................................................................114
Author Contributions to Publication 1 .....................................................................................184
Author Contributions to Publication 2 .....................................................................................186
Author Contributions to Publication 3 .....................................................................................188
Author Contributions to Publication 4 .....................................................................................190
Author Contributions to Publication 5 .....................................................................................191
Declaration of Authenticity ......................................................................................................193
Curriculum Vitae ......................................................................................................................194
List of Publications ................................................................................................................195
List of Talks and Posters ......................................................................................................19
Évaluation et modulation des fonctions exécutives en neuroergonomie - Continuums cognitifs et expérimentaux
Des études en neuroergonomie ont montré que le pilote d’avion pouvait commettre des erreurs en raison d’une incapacité transitoire à faire preuve de flexibilité mentale. Il apparait que certains facteurs, tels qu’une forte charge mentale ou une pression temporelle importante, un niveau de stress trop élevé, la survenue de conflits, ou une perte de conscience de la situation, peuvent altérer temporairement l’efficience des fonctions exécutives permettant cette flexibilité. Depuis mes travaux initiaux, dans lesquels je me suis intéressé aux conditions qui conduisent à une négligence auditive, j’ai souhaité développer une approche scientifique visant à quantifier et limiter les effets délétères de ces différents facteurs. Ceci a été fait à travers l’étude des fonctions exécutives chez l’être humain selon le continuum cognitif (du cerveau lésé au cerveau en parfait état de fonctionnement) et le continuum expérimental (de l’ordinateur au monde réel). L’approche fondamentale de l’étude des fonctions exécutives en neurosciences combinée à l’approche neuroergonomique graduelle avec des pilotes et des patients cérébro-lésés, a permis de mieux comprendre la manière dont ces fonctions sont mises en jeu et altérées. Cette connaissance à contribuer par la suite à la mise en place de solutions pour préserver leur efficacité en situation complexe.
Après avoir rappelé mon parcours académique, je présente dans ce manuscrit une sélection de travaux répartis sur trois thématiques de recherche. La première concerne l’étude des fonctions exécutives impliquées dans l’attention et en particulier la façon dont la charge perceptive et la charge mentale peuvent altérer ces fonctions. La deuxième correspond à un aspect plus appliqué de ces travaux avec l’évaluation de l’état du pilote. Il a été question d’analyser cet état selon l’activité de pilotage elle-même ou à travers la gestion et la supervision d’un système en particulier. La troisième et dernière thématique concerne la recherche de marqueurs prédictifs de la performance cognitive et l’élaboration d’entraînements cognitifs pour limiter les troubles dysexécutifs, qu’ils soient d’origine contextuelle ou lésionnelle.
Ces travaux ont contribué à une meilleure compréhension des troubles cognitifs transitoires ou chroniques, mais ils ont aussi soulevé des questions auxquelles je souhaite répondre aujourd’hui. Pour illustrer cette réflexion, je présente en dernière partie de ce document mon projet de recherche qui vise à développer une approche multifactorielle de l’efficience cognitive, éthique et en science ouverte
Relationship between Anxiety and Freezing of Gait
Parkinson’s disease (PD) is the second most common neurodegenerative and a large percentage of PD patients develop freezing of gait (FOG) leading to an overall reduced quality of life. The overarching aim of the thesis is to investigate the relationship between anxiety and freezing of gait, to extend current research on this topic and produce findings that could facilitate more adequate treatment methods for this symptom.
The first study validated the seated functional MRI-compatible version of the walking threat paradigm that was previously found to induce anxiety and FOG. This would enable future studies to examine the neural correlates behind anxiety-induced freezing of gait. The second study investigated the effect of anxiety on the utilisation of body-related visual feedback in the form of an avatar in the virtual environment to improve FOG. The third study investigated the effects of Levodopa on the fronto-striato-limbic circuitry in PD Freezers at rest in their ‘ON’ and ‘OFF’ dopaminergic state.
Findings suggest that the VR seated threat paradigm is an adequate behavioural surrogate for the VR walking threat paradigm, eliciting comparable amounts of anxiety and freezing of gait as the walking version. Anxiety was also found to interfere with the utilisation of sensory feedback to improve FOG, where in highly threatening situations Freezers lack the capacity to process visual feedback for gait. Finally, dopaminergic medication was also found to partially modulate the frontoparietal-limbic-striatal circuitry in PD Freezers, where baseline anxiety levels influence the impact of Levodopa on the frontoparietal (FPN)- limbic connectivity, and the FPN-putamen connectivity.
In conclusion, the current thesis suggests that anxiety contributes to freezing of gait, which may present a barrier to treatment and could be a key factor in the heterogeneity observed in response to medication and sensory cueing
A novel optogenetics-based therapy for obstructive sleep apnoea
Obstructive sleep apnoea (OSA) is characterised by repeat upper airway narrowing and/or collapse during sleep. Many patients are sub-optimally treated due to poor tolerance or incomplete response to established therapies. We propose a novel, optogenetics-based therapy, that enables light-stimulation induced upper airway dilator muscle contractions to maintain airway patency.
The primary aims of this thesis were to determine feasibility in a rodent model of OSA, and identify effective optogenetic constructs for activating upper airway muscles. Chapters 2 and 3 outline the development of a novel construct for the expression of light-sensitive proteins (opsins) in upper airway muscles, comparing two promotors and two recombinant adeno-associated virus capsids (rAAV) for optogenetic gene transfer. Results show that a muscle-specific promotor (tMCK) was superior to a non-specific promotor (CAG). With tMCK, opsin expression in the tongue was 470% greater (p=0.013, RM-ANOVA), brainstem expression was abolished, and light stimulation facilitated a 66% increase in muscle activity from that recorded during unstimulated breaths in an acute model of OSA (p<0.001, linear mixed model) (Chapter 2). Moreover, a novel, highly myotropic rAAV serotype, AAVMYO, was superior to a wild-type serotype, AAV9. The AAVMYO serotype driven by tMCK facilitated a further increase in muscle activity with light stimulation to 194% of that recorded during unstimulated breaths (p<0.001, linear mixed model) (Chapter 3). Finally, ultrasound imaging confirmed that the optimised construct was able to generate effective light-induced muscle contractions and airway dilation (Chapter 4).
A secondary aim was to advance preclinical trials for the proposed therapy. To this end, a surgical protocol for chronic implantation of light delivery hardware and recording electrodes in rodents was developed (Chapter 5). The final protocol will allow us to determine the effects of acute and chronic light stimulation on opsin-expressing upper airway muscles during natural sleep.
In summary, Chapters 2 to 4 provide proof-of-concept for a non-invasive optogenetics-based OSA therapy. The combination of a muscle-specific promotor and a muscle-specific viral vector presents a novel and highly effective method of inducing light sensitivity into skeletal muscle and facilitating light-evoked airway dilation. Finally, Chapter 5 commences the development of a surgical protocol that will aid ongoing preclinical trials
Water and Brain Function: Effects of Hydration Status on Neurostimulation and Neurorecording
Introduction: TMS and EEG are used to study normal neurophysiology, diagnose, and treat clinical neuropsychiatric conditions, but can produce variable results or fail. Both techniques depend on electrical volume conduction, and thus brain volumes. Hydration status can affect brain volumes and functions (including cognition), but effects on these techniques are unknown. We aimed to characterize the effects of hydration on TMS, EEG, and cognitive tasks. Methods: EEG and EMG were recorded during single-pulse TMS, paired-pulse TMS, and cognitive tasks from 32 human participants on dehydrated (12-hour fast/thirst) and rehydrated (1 Liter oral water ingestion in 1 hour) testing days. Hydration status was confirmed with urinalysis. MEP, ERP, and network analyses were performed to examine responses at the muscle, brain, and higher-order functioning. Results: Rehydration decreased motor threshold (increased excitability) and shifted the motor hotspot. Significant effects on TMS measures occurred despite being re-localized and re-dosed to these new parameters. Rehydration increased SICF of the MEP, magnitudes of specific TEP peaks in inhibitory protocols, specific ERP peak magnitudes and reaction time during the cognitive task. Rehydration amplified nodal inhibition around the stimulation site in inhibitory paired-pulse networks and strengthened nodes outside the stimulation site in excitatory and CSP networks. Cognitive performance was not improved by rehydration, although similar performance was achieved with generally weaker network activity. Discussion: Results highlight differences between mild dehydration and rehydration. The rehydrated brain was easier to stimulate with TMS and produced larger responses to external and internal stimuli. This is explainable by the known physiology of body water dynamics, which encompass macroscopic and microscopic volume changes. Rehydration can shift 3D cortical positioning, decrease scalp cortex distance (bringing cortex closer to stimulator/recording electrodes), and cause astrocyte swelling-induced glutamate release. Conclusions: Previously unaccounted variables like osmolarity, astrocyte and brain volumes likely affect neurostimulation/neurorecording. Controlling for and carefully manipulating hydration may reduce variability and improve therapeutic outcomes of neurostimulation. Dehydration is common and produces less excitable circuits. Rehydration should offer a mechanism to macroscopically bring target cortical areas closer to an externally applied neurostimulation device to recruit greater volumes of tissue and microscopically favor excitability in the stimulated circuits
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