2,367 research outputs found

    Computational techniques to interpret the neural code underlying complex cognitive processes

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    Advances in large-scale neural recording technology have significantly improved the capacity to further elucidate the neural code underlying complex cognitive processes. This thesis aimed to investigate two research questions in rodent models. First, what is the role of the hippocampus in memory and specifically what is the underlying neural code that contributes to spatial memory and navigational decision-making. Second, how is social cognition represented in the medial prefrontal cortex at the level of individual neurons. To start, the thesis begins by investigating memory and social cognition in the context of healthy and diseased states that use non-invasive methods (i.e. fMRI and animal behavioural studies). The main body of the thesis then shifts to developing our fundamental understanding of the neural mechanisms underpinning these cognitive processes by applying computational techniques to ana lyse stable large-scale neural recordings. To achieve this, tailored calcium imaging and behaviour preprocessing computational pipelines were developed and optimised for use in social interaction and spatial navigation experimental analysis. In parallel, a review was conducted on methods for multivariate/neural population analysis. A comparison of multiple neural manifold learning (NML) algorithms identified that non linear algorithms such as UMAP are more adaptable across datasets of varying noise and behavioural complexity. Furthermore, the review visualises how NML can be applied to disease states in the brain and introduces the secondary analyses that can be used to enhance or characterise a neural manifold. Lastly, the preprocessing and analytical pipelines were combined to investigate the neural mechanisms in volved in social cognition and spatial memory. The social cognition study explored how neural firing in the medial Prefrontal cortex changed as a function of the social dominance paradigm, the "Tube Test". The univariate analysis identified an ensemble of behavioural-tuned neurons that fire preferentially during specific behaviours such as "pushing" or "retreating" for the animal’s own behaviour and/or the competitor’s behaviour. Furthermore, in dominant animals, the neural population exhibited greater average firing than that of subordinate animals. Next, to investigate spatial memory, a spatial recency task was used, where rats learnt to navigate towards one of three reward locations and then recall the rewarded location of the session. During the task, over 1000 neurons were recorded from the hippocampal CA1 region for five rats over multiple sessions. Multivariate analysis revealed that the sequence of neurons encoding an animal’s spatial position leading up to a rewarded location was also active in the decision period before the animal navigates to the rewarded location. The result posits that prospective replay of neural sequences in the hippocampal CA1 region could provide a mechanism by which decision-making is supported

    Characterizing Sleep Patterns in Youth with CP and its Impact on Mood

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    Background. Cerebral palsy (CP) is a lifelong neurodevelopmental condition characterized by limitations in movement and posture (Oskoui et al., 2013; Rosenbaum et al., 2007). There is a growing consensus that sleep difficulties are common and life-long in individuals with CP (Lélis et al., 2016; Newman et al., 2006; Simard-Tremblay et al., 2011). These difficulties encompass various aspects such as sleep duration, sleep quality, staying asleep, and experiencing more difficulty getting up in the morning (Lélis et al., 2016; Newman et al., 2006); however, much remains unknown about the specific sleep patterns in CP and whether they are distinct from those observed in other conditions such as autism or fetal alcohol spectrum disorder (FASD). Additionally, the link between sleep and mood in CP is not well understood (Gadie et al., 2017). While in neurotypical youth, better sleep has been linked to improvements in social, emotional, and psychological well-being (e.g., mood), the extent to which sleep may impact mood within the context of CP remains uncertain (Hamilton et al., 2007). This manuscript-based thesis aims to address these significant gaps in knowledge by examining the sleep patterns in youth with CP and investigate the subsequent temporal association between sleep and mood. Methods. For this exploratory manuscript-based thesis, we analyzed secondary data from baseline questionnaires and weekly data (accelerometers and daily sleep diaries) collected from a larger study that examined the associations between physiological factors and mental health in youth with CP. In the first study, we investigated the sleep patterns of 45 youth with CP using caregiver and youth reports, the Child/Adolescent Sleep-Wake Scale (CSWS/ASWS), Insomnia Severity Index (ISI), and measurements from actigraphs that youth wore for one week. First, the sleep characteristics were described in relation to available demographic variables (e.g., sex, age, Gross Motor Functioning Classification System level [GMFCS]), using descriptive statistics. Second, to determine the impact of the presence of a mental health diagnosis on sleep patterns and problems, a hierarchical regression analyses was conducted. In the second study, we focused on a subsample of youth (n = 32) who had sufficient daily diaries of sleep and mood. In paper 2, the impact of intraindividual variability (IIV) in sleep patterns on mood (i.e., positive and negative affect) was examined using a series of fixed-effects multi-level modelling. Analyses included age, sex, and GMFCS as covariates as these factors contribute to sleep and mood. Results. In the first study of 45 youth, the average sleep duration was 10 hours per night (SD = 0:59), ranging from 7.5 to 12.85 hours. Youth experienced an average of 14 awakenings (>5 min) per night (SD = 5.3), which is substantially higher than previous literature in youth without CP. Most youth reported poor sleep quality based on sleep quality scores from the combined CSWS and ASWS (M = 3.67, SD = 1.24). Hierarchical linear regression analysis revealed a significant positive association between mental health diagnosis and insomnia severity, even after controlling for participant demographics (age, sex, GMFCS) (p = .010). For the second study, fixed-effect models were used to examine the association between IIV sleep duration and quality and next-day negative and positive affect over a 7-day period. While controlling for covariates, higher within-subjects variability of sleep quality was related to lower next-day negative mood (b = -.03, p < .001) and increased next-day positive mood (b = .05, p = .018). To determine the directionality of this association, mood variability predicting next day sleep was examined; however, only higher within-subject variability of negative mood was related to next-day sleep quality (b = -1.12, p = .011). Conclusions. This thesis is the first of its kind to examine the group and individual characteristics of sleep patterns among youth with CP (Study 1) and the temporal impact of IIV sleep on daily positive and negative affect (Study 2). Sleep is a complex phenomenon, and further investigation is necessary to understand the influence of various other factors, which were not available for this thesis. Nevertheless, sleep timing and sleep consistency may be important characteristics of sleep health. Overall, more research is needed to help inform prevention of mental health issues in this already vulnerable population and to help inform the development of supports for sleep

    Post-stroke upper limb recovery is correlated with dynamic resting-state network connectivity

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    Motor recovery is still limited for people with stroke especially those with greater functional impairments. In order to improve outcome, we need to understand more about the mechanisms underpinning recovery. Task-unbiased, blood-flow independent post-stroke neural activity can be acquired from resting brain electrophysiological recordings, and offers substantial promise to investigate physiological mechanisms, but behaviourally-relevant features of resting-state sensorimotor network dynamics have not yet been identified. Thirty-seven people with subcortical ischemic stroke and unilateral hand paresis of any degree were longitudinally evaluated at 3 weeks (early subacute) and 12 weeks (late subacute) after stroke. Resting-state magnetoencephalography and clinical scores of motor function were recorded and compared with matched controls. Magnetoencephalography data were decomposed using a data-driven Hidden Markov Model into 10 time-varying resting-state networks. People with stroke showed statistically significantly improved Action Research Arm Test and Fugl-Meyer upper extremity scores between 3 weeks and 12 weeks after stroke (both p &lt; 0.001). Hidden Markov Model analysis revealed a primarily alpha-band ipsilesional resting-state sensorimotor network which had a significantly increased life-time (the average time elapsed between entering and exiting the network) and fractional occupancy (the occupied percentage among all networks) at 3 weeks after stroke when compared to controls. The life-time of the ipsilesional resting-state sensorimotor network positively correlated with concurrent motor scores in people with stroke who had not fully recovered. Specifically, this relationship was observed only in ipsilesional rather in contralesional sensorimotor network, default mode network or visual network. The ipsilesional sensorimotor network metrics were not significantly different from controls at 12 weeks after stroke. The increased recruitment of alpha-band ipsilesional resting-state sensorimotor network at subacute stroke served as functionally correlated biomarkers exclusively in people with stroke with not fully recovered hand paresis, plausibly reflecting functional motor recovery processes

    Speech-based automatic depression detection via biomarkers identification and artificial intelligence approaches

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    Depression has become one of the most prevalent mental health issues, affecting more than 300 million people all over the world. However, due to factors such as limited medical resources and accessibility to health care, there are still a large number of patients undiagnosed. In addition, the traditional approaches to depression diagnosis have limitations because they are usually time-consuming, and depend on clinical experience that varies across different clinicians. From this perspective, the use of automatic depression detection can make the diagnosis process much faster and more accessible. In this thesis, we present the possibility of using speech for automatic depression detection. This is based on the findings in neuroscience that depressed patients have abnormal cognition mechanisms thus leading to the speech differs from that of healthy people. Therefore, in this thesis, we show two ways of benefiting from automatic depression detection, i.e., identifying speech markers of depression and constructing novel deep learning models to improve detection accuracy. The identification of speech markers tries to capture measurable depression traces left in speech. From this perspective, speech markers such as speech duration, pauses and correlation matrices are proposed. Speech duration and pauses take speech fluency into account, while correlation matrices represent the relationship between acoustic features and aim at capturing psychomotor retardation in depressed patients. Experimental results demonstrate that these proposed markers are effective at improving the performance in recognizing depressed speakers. In addition, such markers show statistically significant differences between depressed patients and non-depressed individuals, which explains the possibility of using these markers for depression detection and further confirms that depression leaves detectable traces in speech. In addition to the above, we propose an attention mechanism, Multi-local Attention (MLA), to emphasize depression-relevant information locally. Then we analyse the effectiveness of MLA on performance and efficiency. According to the experimental results, such a model can significantly improve performance and confidence in the detection while reducing the time required for recognition. Furthermore, we propose Cross-Data Multilevel Attention (CDMA) to emphasize different types of depression-relevant information, i.e., specific to each type of speech and common to both, by using multiple attention mechanisms. Experimental results demonstrate that the proposed model is effective to integrate different types of depression-relevant information in speech, improving the performance significantly for depression detection

    Life on a scale:Deep brain stimulation in anorexia nervosa

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    Anorexia nervosa (AN) is a severe psychiatric disorder marked by low body weight, body image abnormalities, and anxiety and shows elevated rates of morbidity, comorbidity and mortality. Given the limited availability of evidence-based treatments, there is an urgent need to investigate new therapeutic options that are informed by the disorder’s underlying neurobiological mechanisms. This thesis represents the first study in the Netherlands and one of a limited number globally to evaluate the efficacy, safety, and tolerability of deep brain stimulation (DBS) in the treatment of AN. DBS has the advantage of being both reversible and adjustable. Beyond assessing the primary impact of DBS on body weight, psychological parameters, and quality of life, this research is novel in its comprehensive approach. We integrated evaluations of efficacy with critical examinations of the functional impact of DBS in AN, including fMRI, electroencephalography EEG, as well as endocrinological and metabolic assessments. Furthermore, this work situates AN within a broader theoretical framework, specifically focusing on its manifestation as a form of self-destructive behavior. Finally, we reflect on the practical, ethical and philosophical aspects of conducting an experimental, invasive procedure in a vulnerable patient group. This thesis deepens our understanding of the neurobiological underpinnings of AN and paves the way for future research and potential clinical applications of DBS in the management of severe and enduring AN

    Differences in well-being:the biological and environmental causes, related phenotypes, and real-time assessment

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    Well-being is a complex, and multifaceted construct that includes feeling good and functioning well. There is a growing global recognition of well-being as an important research topic and public policy goal. Well-being is related to less behavioral and emotional problems, and is associated with many positive aspects of daily life, including longevity, higher educational achievement, happier marriage, and more productivity at work. People differ in their levels of well-being, i.e., some people are in general happier or more satisfied with their lives than others. These individual differences in well-being can arise from many different factors, including biological (genetic) influences and environmental influences. To enhance the development of future mental health prevention and intervention strategies to increase well-being, more knowledge about these determinants and factors underlying well-being is needed. In this dissertation, I aimed to increase the understanding of the etiology in a series of studies using different methods, including systematic reviews, meta-analyses, twin designs, and molecular genetic designs. In part I, we brought together all published studies on the neural and physiological factors underlying well-being. This overview allowed us to critically investigate the claims made about the biology involved in well-being. The number of studies on the neural and physiological factors underlying well-being is increasing and the results point towards potential correlates of well-being. However, samples are often still small, and studies focus mostly on a single biomarker. Therefore, more well-powered, data-driven, and integrative studies across biological categories are needed to better understand the neural and physiological pathways that play a role in well-being. In part II, we investigated the overlap between well-being and a range of other phenotypes to learn more about the etiology of well-being. We report a large overlap with phenotypes including optimism, resilience, and depressive symptoms. Furthermore, when removing the genetic overlap between well-being and depressive symptoms, we showed that well-being has unique genetic associations with a range of phenotypes, independently from depressive symptoms. These results can be helpful in designing more effective interventions to increase well-being, taking into account the overlap and possible causality with other phenotypes. In part III, we used the extreme environmental change during the COVID-19 pandemic to investigate individual differences in the effects of such environmental changes on well-being. On average, we found a negative effect of the pandemic on different aspects of well-being, especially further into the pandemic. Whereas most previous studies only looked at this average negative effect of the pandemic on well-being, we focused on the individual differences as well. We reported large individual differences in the effects of the pandemic on well-being in both chapters. This indicates that one-size-fits-all preventions or interventions to maintain or increase well-being during the pandemic or lockdowns will not be successful for the whole population. Further research is needed for the identification of protective factors and resilience mechanisms to prevent further inequality during extreme environmental situations. In part IV, we looked at the real-time assessment of well-being, investigating the feasibility and results of previous studies. The real-time assessment of well-being, related variables, and the environment can lead to new insights about well-being, i.e., results that we cannot capture with traditional survey research. The real-time assessment of well-being is therefore a promising area for future research to unravel the dynamic nature of well-being fluctuations and the interaction with the environment in daily life. Integrating all results in this dissertation confirmed that well-being is a complex human trait that is influenced by many interrelated and interacting factors. Future directions to understand individual differences in well-being will be a data-driven approach to investigate the complex interplay of neural, physiological, genetic, and environmental factors in well-being

    30th European Congress on Obesity (ECO 2023)

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    This is the abstract book of 30th European Congress on Obesity (ECO 2023
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