Unraveling the spatiotemporal brain dynamics during a simulated reach-to-eat task

The reach-to-eat task involves a sequence of action components including looking, reaching, grasping, and feeding. While cortical representations of individual action components have been mapped in human functional magnetic resonance imaging (fMRI) studies, little is known about the continuous spatiotemporal dynamics among these representations during the reach-to-eat task. In a periodic event-related fMRI experiment, subjects were scanned while they reached toward a food image, grasped the virtual food, and brought it to their mouth within each 16-s cycle. Fourier-based analysis of fMRI time series revealed periodic signals and noise distributed across the brain. Independent component analysis was used to remove periodic or aperiodic motion artifacts. Timefrequency analysis was used to analyze the temporal characteristics of periodic signals in each voxel. Circular statistics was then used to estimate mean phase angles of periodic signals and select voxels based on the distribution of phase angles. By sorting mean phase angles across regions, we were able to show the real-time spatiotemporal brain dynamics as continuous traveling waves over the cortical surface. The activation sequence consisted of approximately the following stages: (1) stimulus related activations in occipital and temporal cortices; (2) movement planning related activations in dorsal premotor and superior parietal cortices; (3) reaching related activations in primary sensorimotor cortex and supplementary motor area; (4) grasping related activations in postcentral gyrus and sulcus; (5) feeding related activations in orofacial areas. These results suggest that phase-encoded design and analysis can be used to unravel sequential activations among brain regions during a simulated reach-to-eat task

Cell Migration within 3D Microenvironments: an Integrative Perspective from the Membrane to the Nucleus

La migración celular es fundamental para la vida y el desarrollo. Desafortunadamente, la movilidad celular también está asociada con algunas de las principales causas de morbilidad y mortalidad, incluidos los trastornos inmunitarios, esqueléticos y cardiovasculares, así como la metástasis del cáncer. Las células dependen en su capacidad para percibir y responder a estímulos externos en muchos procesos fisiológicos y patológicos (p. ej., desarrollo embrionario, angiogénesis, reparación de tejidos y progresión tumoral). El objetivo global de esta tesis doctoral fue investigar la respuesta migratoria de células individuales a señales bioquímicas y biofísicas. En particular, el enfoque de esta investigación se centró en los mecanismos que permiten a las células percibir e internalizar señales bioquímicas y biofísicas y la influencia de estos estímulos en la respuesta migratoria de las células individuales.El primer estudio tuvo como objetivo establecer una metodología para facilitar la integración de estudios teóricos con datos experimentales. Al minimizar la intervención del usuario, el sistema propuesto basado en técnicas de optimización Bayesiana gestionó de manera eficiente la calibración de los modelos in silico, que de otro modo sería tediosa y propensa a errores. Posteriormente, se construyó un modelo in silico para investigar cómo los estímulos bioquímicos y biofísicos influyen en el movimiento celular en tres dimensiones. Este modelo computacional integró algunos de los principales actores que permiten a las células percibir y responder a señales externas, que pueden actuar a diferentes escalas e interactuar entre sí. Los resultados mostraron, por un lado, que las células cambian su comportamiento migratorio en función de la pendiente de los gradientes químicos y la concentración absoluta de factores químicos (por ejemplo, factores de crecimiento) a su alrededor. Por otro lado, estos resultados revelaron que la respuesta migratoria de las células a la rigidez y densidad de la matriz depende de su fenotipo. En general, la tesis destaca la dependencia de la migración celular tridimensional al fenotipo de las células (es decir, el tamaño de su núcleo, la deformabilidad del mismo) y las propiedades del microambiente circundante (por ejemplo, el perfil químico, la rigidez de la matriz, el confinamiento).Cell migration is fundamental for life and development. Unfortunately, cell motility is also associated with some of the leading causes of morbidity and mortality, including immune, skeletal, and cardiovascular disorders as well as cancer metastasis. Cells rely on their ability to perceive and respond to external stimuli in many physiological and pathological processes (e.g., embryonic development, angiogenesis, tissue repair, and tumor progression). The global objective of this doctoral thesis was to investigate the migratory response of individual cells to biochemical and biophysical cues. In particular, the focus of this research was on the mechanisms enabling cells to perceive and internalize biochemical and biophysical cues and the influence of these stimuli on the migratory response of individual cells. The first study aimed at establishing a methodology to facilitate the integration of theoretical studies with experimental data. By minimizing user intervention, the proposed framework based on Bayesian optimization techniques efficiently handled the otherwise tedious and error-prone calibration of in silico models. Afterward, an in silico model was built to investigate how biochemical and biophysical stimuli influence three-dimensional cell motion. This computational model integrated some of the main actors enabling cells to probe and respond to external cues, which may act at different scales and interact with each other. The results showed, on the one hand, that cells change their migratory behavior based on the slope of chemical gradients and the absolute concentration of chemical factors (e.g., growth factors) around them. On the other hand, these results revealed that cells’ migratory response to matrix stiffness and density depends on their phenotype. Overall, this thesis highlights the dependence of three-dimensional cell migration on both cells’ phenotype (i.e., nucleus size, deformability) and the properties of the surrounding microenvironment (e.g., chemical profile, matrix rigidity, confinement).<br /

How hand movements and speech tip the balance in cognitive development:A story about children, complexity, coordination, and affordances

When someone asks us to explain something, such as how a lever or balance scale works, we spontaneously move our hands and gesture. This is also true for children. Furthermore, children use their hands to discover things and to find out how something works. Previous research has shown that children’s hand movements hereby are ahead of speech, and play a leading role in cognitive development. Explanations for this assumed that cognitive understanding takes place in one’s head, and that hand movements and speech (only) reflect this. However, cognitive understanding arises and consists of the constant interplay between (hand) movements and speech, and someone’s physical and social environment. The physical environment includes task properties, for example, and the social environment includes other people. Therefore, I focused on this constant interplay between hand movements, speech, and the environment, to better understand hand movements’ role in cognitive development. Using science and technology tasks, we found that children’s speech affects hand movements more than the other way around. During difficult tasks the coupling between hand movements and speech becomes even stronger than in easy tasks. Interim changes in task properties differently affect hand movements and speech. Collaborating children coordinate their hand movements and speech, and even their head movements together. The coupling between hand movements and speech is related to age and (school) performance. It is important that teachers attend to children’s hand movements and speech, and arrange their lessons and classrooms such that there is room for both

Simulations and Modelling for Biological Invasions

Biological invasions are characterized by the movement of organisms from their native geographic region to new, distinct regions in which they may have significant impacts. Biological invasions pose one of the most serious threats to global biodiversity, and hence significant resources are invested in predicting, preventing, and managing them. Biological systems and processes are typically large, complex, and inherently difficult to study naturally because of their immense scale and complexity. Hence, computational modelling and simulation approaches can be taken to study them. In this dissertation, I applied computer simulations to address two important problems in invasion biology. First, in invasion biology, the impact of genetic diversity of introduced populations on their establishment success is unknown. We took an individual-based modelling approach to explore this, leveraging an ecosystem simulation called EcoSim to simulate biological invasions. We conducted reciprocal transplants of prey individuals across two simulated environments, over a gradient of genetic diversity. Our simulation results demonstrated that a harsh environment with low and spatially-varying resource abundance mediated a relationship between genetic diversity and short-term establishment success of introduced populations rather than the degree of difference between native and introduced ranges. We also found that reducing Allee effects by maintaining compactness, a measure of spatial density, was key to the establishment success of prey individuals in EcoSim, which were sexually reproducing. Further, we found evidence of a more complex relationship between genetic diversity and long-term establishment success, assuming multiple introductions were occurring. Low-diversity populations seemed to benefit more strongly from multiple introductions than high-diversity populations. Our results also corroborated the evolutionary imbalance hypothesis: the environment that yielded greater diversity produced better invaders and itself was less invasible. Finally, our study corroborated a mechanical explanation for the evolutionary imbalance hypothesis – the populations evolved in a more intense competitive environment produced better invaders. Secondly, an important advancement in invasion biology is the use of genetic barcoding or metabarcoding, in conjunction with next-generation sequencing, as a potential means of early detection of aquatic introduced species. Barcoding and metabarcoding invariably requires some amount of computational DNA sequence processing. Unfortunately, optimal processing parameters are not known in advance and the consequences of suboptimal parameter selection are poorly understood. We aimed to determine the optimal parameterization of a common sequence processing pipeline for both early detection of aquatic nonindigenous species and conducting species richness assessments. We then aimed to determine the performance of optimized pipelines in a simulated inoculation of sequences into community samples. We found that early detection requires relatively lenient processing parameters. Further, optimality depended on the research goal – what was optimal for early detection was suboptimal for estimating species richness and vice-versa. Finally, with optimal parameter selection, fewer than 11 target sequences were required in order to detect 90% of nonindigenous species

Engineering derivatives from biological systems for advanced aerospace applications

The present study consisted of a literature survey, a survey of researchers, and a workshop on bionics. These tasks produced an extensive annotated bibliography of bionics research (282 citations), a directory of bionics researchers, and a workshop report on specific bionics research topics applicable to space technology. These deliverables are included as Appendix A, Appendix B, and Section 5.0, respectively. To provide organization to this highly interdisciplinary field and to serve as a guide for interested researchers, we have also prepared a taxonomy or classification of the various subelements of natural engineering systems. Finally, we have synthesized the results of the various components of this study into a discussion of the most promising opportunities for accelerated research, seeking solutions which apply engineering principles from natural systems to advanced aerospace problems. A discussion of opportunities within the areas of materials, structures, sensors, information processing, robotics, autonomous systems, life support systems, and aeronautics is given. Following the conclusions are six discipline summaries that highlight the potential benefits of research in these areas for NASA's space technology programs

Mind in Action: Action Representation and the Perception of Biological Motion

The ability to understand and communicate about the actions of others is a fundamental aspect of our daily activity. How can we talk about what others are doing? What qualities do different actions have such that they cause us to see them as being different or similar? What is the connection between what we see and the development of concepts and words or expressions for the things that we see? To what extent can two different people see and talk about the same things? Is there a common basis for our perception, and is there then a common basis for the concepts we form and the way in which the concepts become lexicalized in language? The broad purpose of this thesis is to relate aspects of perception, categorization and language to action recognition and conceptualization. This is achieved by empirically demonstrating a prototype structure for action categories and by revealing the effect this structure has on language via the semantic organization of verbs for natural actions. The results also show that implicit access to categorical information can affect the perceptual processing of basic actions. These findings indicate that our understanding of human actions is guided by the activation of high level information in the form of dynamic action templates or prototypes. More specifically, the first two empirical studies investigate the relation between perception and the hierarchical structure of action categories, i.e., subordinate, basic, and superordinate level action categories. Subjects generated lists of verbs based on perceptual criteria. Analyses based on multidimensional scaling showed a significant correlation for the semantic organization of a subset of the verbs for English and Swedish speaking subjects. Two additional experiments were performed in order to further determine the extent to which action categories exhibit graded structure, which would indicate the existence of prototypes for action categories. The results from typicality ratings and category verification showed that typicality judgments reliably predict category verification times for instances of different actions. Finally, the results from a repetition (short-term) priming paradigm suggest that high level information about the categorical differences between actions can be implicitly activated and facilitates the later visual processing of displays of biological motion. This facilitation occurs for upright displays, but appears to be lacking for displays that are shown upside down. These results show that the implicit activation of information about action categories can play a critical role in the perception of human actions

Neuronal underpinning of reproductive state dependent olfactory behavior in Drosophila

A general question in neuroscience is how the flow of sensory information is encoded towards a behavioral response. These behavioral responses can be interpreted as decisions the organism needs to make to get a most beneficial outcome. Factors which can influence these decisions can be external or internal. Considering sensory information, external stimuli can elicit "innate" responses to a sensory input, which lead to a certain behavior. Interestingly, these responses can be overwritten given a certain experience or context. The internal state of an organism can be such a context. Internal states, such as age, stress, hunger, or reproductive state can have effects on chemosensory decision making behavior. Such behavior usually manifests itself by attraction or aversion towards a certain odor or taste. Occasionally, transient neuromodulation can affect these behaviors, by focusing an animal's attention to relevant sensory stimuli in its environment. This might facilitate remembering relevant vs. irrelevant stimuli. Here, we are investigating the role of such a sensory neuromodulation and the formation of memory in the female fruit fly, Drosophila melanogaster. Previous work from our lab has shown that mating changes the sensitivity of olfactory and gustatory neurons with the help of specific neuromodulators that act directly on these chemosensory neurons. However, this very transient neuromodulation leads to a long-term behavioral change in females: for instance, while virgin flies usually prefer low concentrations of polyamines, mated flies will prefer higher concentrations after the mating experience and will continue this behavior for up to two weeks until falling back to a virgin-like state. Drosophila's genetic toolset allows us to test the hypothesis that this transient sensory enhancement facilitates the formation of a long-lasting memory. Using a quantitative olfactory choice assay, my collaborators and I silenced and activated neuronal activity in different parts of the fly's associative memory center (i.e. the mushroom body). We revealed a possible neuronal pathway and its modulatory switch between virgin and mated state. These findings suggest that dopaminergic neurons, which are innervating the mushroom body, control virgin vs. mated female behavior by processing sensory input differentially before and after mating, respectively. Furthermore, our data suggests that courtship and pheromones are highly important signals to trigger the reproductive state dependent change in olfactory preference behavior. In addition, my collaborators and I wanted to use state-of-the-art techniques to shed light on the detection of nutrients valuable for the gravid fly by using bioinformatic tools and to promote these methods to the biological fields. As two-photon laser scanning microscopy is an important tool for neuroscientific research in the fly and beyond, I built such a microscope. Harnessing this experience, I have, in collaboration, written a guide for life scientists wishing to build or purchase such a microscope. A joint effort between established behavioral assays and technological advances, such as bioinformatic tools, can support and extend our understanding of neuronal circuits underlying reproductive state dependent behaviors

Neuronal underpinning of reproductive state dependent olfactory behavior in Drosophila

A general question in neuroscience is how the flow of sensory information is encoded towards a behavioral response. These behavioral responses can be interpreted as decisions the organism needs to make to get a most beneficial outcome. Factors which can influence these decisions can be external or internal. Considering sensory information, external stimuli can elicit "innate" responses to a sensory input, which lead to a certain behavior. Interestingly, these responses can be overwritten given a certain experience or context. The internal state of an organism can be such a context. Internal states, such as age, stress, hunger, or reproductive state can have effects on chemosensory decision making behavior. Such behavior usually manifests itself by attraction or aversion towards a certain odor or taste. Occasionally, transient neuromodulation can affect these behaviors, by focusing an animal's attention to relevant sensory stimuli in its environment. This might facilitate remembering relevant vs. irrelevant stimuli. Here, we are investigating the role of such a sensory neuromodulation and the formation of memory in the female fruit fly, Drosophila melanogaster. Previous work from our lab has shown that mating changes the sensitivity of olfactory and gustatory neurons with the help of specific neuromodulators that act directly on these chemosensory neurons. However, this very transient neuromodulation leads to a long-term behavioral change in females: for instance, while virgin flies usually prefer low concentrations of polyamines, mated flies will prefer higher concentrations after the mating experience and will continue this behavior for up to two weeks until falling back to a virgin-like state. Drosophila's genetic toolset allows us to test the hypothesis that this transient sensory enhancement facilitates the formation of a long-lasting memory. Using a quantitative olfactory choice assay, my collaborators and I silenced and activated neuronal activity in different parts of the fly's associative memory center (i.e. the mushroom body). We revealed a possible neuronal pathway and its modulatory switch between virgin and mated state. These findings suggest that dopaminergic neurons, which are innervating the mushroom body, control virgin vs. mated female behavior by processing sensory input differentially before and after mating, respectively. Furthermore, our data suggests that courtship and pheromones are highly important signals to trigger the reproductive state dependent change in olfactory preference behavior. In addition, my collaborators and I wanted to use state-of-the-art techniques to shed light on the detection of nutrients valuable for the gravid fly by using bioinformatic tools and to promote these methods to the biological fields. As two-photon laser scanning microscopy is an important tool for neuroscientific research in the fly and beyond, I built such a microscope. Harnessing this experience, I have, in collaboration, written a guide for life scientists wishing to build or purchase such a microscope. A joint effort between established behavioral assays and technological advances, such as bioinformatic tools, can support and extend our understanding of neuronal circuits underlying reproductive state dependent behaviors

Error Signals from the Brain: 7th Mismatch Negativity Conference

The 7th Mismatch Negativity Conference presents the state of the art in methods, theory, and application (basic and clinical research) of the MMN (and related error signals of the brain). Moreover, there will be two pre-conference workshops: one on the design of MMN studies and the analysis and interpretation of MMN data, and one on the visual MMN (with 20 presentations). There will be more than 40 presentations on hot topics of MMN grouped into thirteen symposia, and about 130 poster presentations. Keynote lectures by Kimmo Alho, Angela D. Friederici, and Israel Nelken will round off the program by covering topics related to and beyond MMN