Network Properties Revealed during Multi-Scale Calcium Imaging of Seizure Activity in Zebrafish.

Seizures are characterized by hypersynchronization of neuronal networks. Understanding these networks could provide a critical window for therapeutic control of recurrent seizure activity, i.e., epilepsy. However, imaging seizure networks has largely been limited to microcircuits in vitro or small "windows" in vivo. Here, we combine fast confocal imaging of genetically encoded calcium indicator (GCaMP)-expressing larval zebrafish with local field potential (LFP) recordings to study epileptiform events at whole-brain and single-neuron levels in vivo. Using an acute seizure model (pentylenetetrazole, PTZ), we reliably observed recurrent electrographic ictal-like events associated with generalized activation of all major brain regions and uncovered a well-preserved anterior-to-posterior seizure propagation pattern. We also examined brain-wide network synchronization and spatiotemporal patterns of neuronal activity in the optic tectum microcircuit. Brain-wide and single-neuronal level analysis of PTZ-exposed and 4-aminopyridine (4-AP)-exposed zebrafish revealed distinct network dynamics associated with seizure and non-seizure hyperexcitable states, respectively. Neuronal ensembles, comprised of coactive neurons, were also uncovered during interictal-like periods. Taken together, these results demonstrate that macro- and micro-network calcium motifs in zebrafish may provide a greater understanding of epilepsy

VIOLA - A multi-purpose and web-based visualization tool for neuronal-network simulation output

Neuronal network models and corresponding computer simulations are invaluable tools to aid the interpretation of the relationship between neuron properties, connectivity and measured activity in cortical tissue. Spatiotemporal patterns of activity propagating across the cortical surface as observed experimentally can for example be described by neuronal network models with layered geometry and distance-dependent connectivity. The interpretation of the resulting stream of multi-modal and multi-dimensional simulation data calls for integrating interactive visualization steps into existing simulation-analysis workflows. Here, we present a set of interactive visualization concepts called views for the visual analysis of activity data in topological network models, and a corresponding reference implementation VIOLA (VIsualization Of Layer Activity). The software is a lightweight, open-source, web-based and platform-independent application combining and adapting modern interactive visualization paradigms, such as coordinated multiple views, for massively parallel neurophysiological data. For a use-case demonstration we consider spiking activity data of a two-population, layered point-neuron network model subject to a spatially confined excitation originating from an external population. With the multiple coordinated views, an explorative and qualitative assessment of the spatiotemporal features of neuronal activity can be performed upfront of a detailed quantitative data analysis of specific aspects of the data. Furthermore, ongoing efforts including the European Human Brain Project aim at providing online user portals for integrated model development, simulation, analysis and provenance tracking, wherein interactive visual analysis tools are one component. Browser-compatible, web-technology based solutions are therefore required. Within this scope, with VIOLA we provide a first prototype.Comment: 38 pages, 10 figures, 3 table

Investigating computational properties of a neurorobotic closed loop system

This work arises as an attempt to increase and deepen the knowledge of the encoding method of the information by the nervous system. In particular, this study focuses on computational properties of neuronal cultures grown in vitro. Through a neuro-robotic close-loop system composed of either cortical or hippocampal cultures (plated on micro-electrode arrays) on one side and of a robot controlled by the cultures on the other side, it has been possible to analyze experimental dataopenEmbargo per motivi di segretezza e/o di proprietà dei risultati e/o informazioni sensibil

Characterization of polarization sensitive neurons of the central complex in the brain of the desert locust (Schistocerca gregaria)

Charakterisierung von polarisationssensitiven Neuronen des Zentralkomplexes im Gehirn der Wüstenheuschrecke (Schistocerca gregaria)

Electroencephalography brain computer interface using an asynchronous protocol

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, in ful llment of the requirements for the degree of Master of Science. October 31, 2016.Brain Computer Interface (BCI) technology is a promising new channel for communication between humans and computers, and consequently other humans. This technology has the potential to form the basis for a paradigm shift in communication for people with disabilities or neuro-degenerative ailments. The objective of this work is to create an asynchronous BCI that is based on a commercial-grade electroencephalography (EEG) sensor. The BCI is intended to allow a user of possibly low income means to issue control signals to a computer by using modulated cortical activation patterns as a control signal. The user achieves this modulation by performing a mental task such as imagining waving the left arm until the computer performs the action intended by the user. In our work, we make use of the Emotiv EPOC headset to perform the EEG measurements. We validate our models by assessing their performance when the experimental data is collected using clinical-grade EEG technology. We make use of a publicly available data-set in the validation phase. We apply signal processing concepts to extract the power spectrum of each electrode from the EEG time-series data. In particular, we make use of the fast Fourier transform (FFT). Specific bands in the power spectra are used to construct a vector that represents an abstract state the brain is in at that particular moment. The selected bands are motivated by insights from neuroscience. The state vector is used in conjunction with a model that performs classification. The exact purpose of the model is to associate the input data with an abstract classification result which can then used to select the appropriate set of instructions to be executed by the computer. In our work, we make use of probabilistic graphical models to perform this association. The performance of two probabilistic graphical models is evaluated in this work. As a preliminary step, we perform classification on pre-segmented data and we assess the performance of the hidden conditional random fields (HCRF) model. The pre-segmented data has a trial structure such that each data le contains the power spectra measurements associated with only one mental task. The objective of the assessment is to determine how well the HCRF models the spatio-spectral and temporal relationships in the EEG data when mental tasks are performed in the aforementioned manner. In other words, the HCRF is to model the internal dynamics of the data corresponding to the mental task. The performance of the HCRF is assessed over three and four classes. We find that the HCRF can model the internal structure of the data corresponding to different mental tasks. As the final step, we perform classification on continuous data that is not segmented and assess the performance of the latent dynamic conditional random fields (LDCRF). The LDCRF is used to perform sequence segmentation and labeling at each time-step so as to allow the program to determine which action should be taken at that moment. The sequence segmentation and labeling is the primary capability that we require in order to facilitate an asynchronous BCI protocol. The continuous data has a trial structure such that each data le contains the power spectra measurements associated with three different mental tasks. The mental tasks are randomly selected at 15 second intervals. The objective of the assessment is to determine how well the LDCRF models the spatio-spectral and temporal relationships in the EEG data, both within each mental task and in the transitions between mental tasks. The performance of the LDCRF is assessed over three classes for both the publicly available data and the data we obtained using the Emotiv EPOC headset. We find that the LDCRF produces a true positive classification rate of 82.31% averaged over three subjects, on the validation data which is in the publicly available data. On the data collected using the Emotiv EPOC, we find that the LDCRF produces a true positive classification rate of 42.55% averaged over two subjects. In the two assessments involving the LDCRF, the random classification strategy would produce a true positive classification rate of 33.34%. It is thus clear that our classification strategy provides above random performance on the two groups of data-sets. We conclude that our results indicate that creating low-cost EEG based BCI technology holds potential for future development. However, as discussed in the final chapter, further work on both the software and low-cost hardware aspects is required in order to improve the performance of the technology as it relates to the low-cost context.LG201

Design and Validation of Control Interfaces for Anna

This project improves the control mechanisms for a semi-autonomous wheelchair with an assistive robotic arm system. The wheelchair is aimed at increasing the self-sufficiency of individuals with LIS. The objectives include the validation of the existing control interfaces, as well as the integration and design of new systems. The wireless brain-computer headset, used to implement the control system for navigation, is validated through several user studies. An EMG sensor system serves as an alternative control module. To increase physical interaction with the environment, a robotic arm system is integrated. The system includes a RGB-D camera for object detection, enabling autonomous object retrieval. The project outcomes include a demonstration performing navigation and manipulation tasks

Processing of Polarization Patterns and Visual Self-Motion in the Locust Central Complex for Spatial Orientation

Despite their relatively small brains with comparatively low neuron counts, insects show complex navigation behavior such as seasonal long-range migration, path integration, and precise straight-line movement. Spatial navigation requires a sense of current heading, which must be tethered to prominent external cues and updated by internal cues that result from movement. Global external cues such as the position of the sun may provide a reference frame for orientation. Sunlight is polarized by scattering in the atmosphere, which results in a sky-spanning polarization pattern that directly depends on the current solar position and makes polarization information, like the sun itself, useful as an external reference cue. Internally, moving through the environment generates optic flow---the motion of the viewed scenery on the retina---, which may inform about turning maneuvers, movement speed, and covered distance. Many insects use these external and internal cues for orientation, and the neuronal center for spatial navigation likely is the central complex, a higher-order brain structure where sensory information is integrated to form an internal compass representation of the current heading. This thesis addresses the question how celestial compass cues, specifically the polarization pattern, and optic flow are processed in the central complex of the desert locust, a long-range migratory insect. All chapters except the last one are electrophysiological studies in which single central-complex neurons were intracellularly recorded while presenting visual stimuli. The neurons' anatomy was histologically determined by dye injection in order to infer their role in the neural network. The studies in Chapters 1 and 2 show that the central complex contains a neuronal compass that robustly signals the sun direction based on direct sunlight and the integration of the whole solar polarization pattern. This shows that the locust brain uses all available skylight cues in order to form a unified compass signal, enabling robust navigation under different environmental conditions. The study in Chapter 3 further examines how neurons at the input stage of the central complex process skylight cues. Already at this stage, single neurons integrate visual information from large areas of the sky and have receptive fields suitable to build the skylight compass. Chapter 4 sheds light on the detection sensitivity for the angle of polarization, finding that central-complex neurons are highly sensitive in this regard, adapted to analyze the skylight polarization pattern almost in its entirety and under unfavorable environmental conditions. In Chapter 5 the locust central complex was scanned for neurons that receive optic flow information. Neurons at virtually all network stages are sensitive to optic flow, mainly uncoupled from skylight-cue sensitivity. This highlights that sensory information is flexibly processed in the central complex, presumably depending on the animal's current behavioral demands. Further, the study hypothesizes how horizontal turning motion is processed in order to update the internal heading representation, backed up by a computational model that adheres to brain anatomy and physiological data. Altogether, these studies advance the understanding of how external and internal cues are processed in the central-complex network in order to establish a sense of orientation in the insect brain. Finally, I contributed with data sets and programming code to the development of the InsectBrainDatabase (www.insectbraindb.org), a free online database tool designed to manage, share and publish anatomical and functional research data (Chapter 6)

Uncovering the Secrets of the Concept of Place in Cognitive Maps Aided by Artificial Intelligence

Uncovering how mental representations acquire, recall, and decode spatial information about relative locations and environmental attributes (cognitive map) involves different challenges. This work is geared towards theoretical discussions on the controversial issue of cognitive scalability for understanding cognitive map emergence from place and grid cells at the intersection between neuroscience and artificial intelligence. In our view, different place maps emerge from parallel and hierarchical neural structures supporting a global cognitive map. The mechanisms sustaining these maps do not only process sensory input but also assign the input to a location. Contentious issues are presented around these concepts and provide concrete suggestions for moving the field forward. We recommend approaching the described challenges guided by AI-based theoretical aspects of encoded place instead of based chiefly on technological aspects to study the brain. SIGNIFICANCE: A formal difference exists between the concepts of spatial representations between experimental neuroscientists and computer scientists and engineers in the so-called neural-based autonomous navigation field. From a neuroscience perspective, we consider the position of an organism’s body to be entirely determined by translational spatial information (e.g., visited places and velocities). An organism predicts where it is at a specific time using continuous or discrete spatial functions embedded into navigation systems. From these functions, we infer that the concept of place has emerged. However, from an engineering standpoint, we represent structured scaffolds of behavioral processes to determine movements from the organism’s current position to some other spatial locations. These scaffolds are certainly affected by the system’s designer. Therefore, the coding of place, in this case, is predetermined. The contrast between emergent cognitive map through inputs versus predefined spatial recognition between two fields creates an inconsistency. Clarifying this tension can inform us on how the brain encodes abstract knowledge to represent spatial positions, which hints at a universal theory of cognition.Fil: Fernandez Leon, Jose Alberto. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Acosta, Gerardo Gabriel. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentin

The Neural Basis of a Cognitive Map

It has been proposed that as animals explore their environment they build and maintain a cognitive map, an internal representation of their surroundings (Tolman, 1948). We tested this hypothesis using a task designed to assess the ability of rats to make a spatial inference (take a novel shortcut)(Roberts et al., 2007). Our findings suggest that rats are unable to make a spontaneous spatial inference. Furthermore, they bear similarities to experiments which have been similarly unable to replicate or support Tolman’s (1948) findings. An inability to take novel shortcuts suggests that rats do not possess a cognitive map (Bennett, 1996). However, we found evidence of alternative learning strategies, such as latent learning (Tolman & Honzik, 1930b) , which suggest that rats may still be building such a representation, although it does not appear they are able to utilise this information to make complex spatial computations. Neurons found in the hippocampus show remarkable spatial modulation of their firing rate and have been suggested as a possible neural substrate for a cognitive map (O'Keefe & Nadel, 1978). However, the firing of these place cells often appears to be modulated by features of an animal’s behaviour (Ainge, Tamosiunaite, et al., 2007; Wood, Dudchenko, Robitsek, & Eichenbaum, 2000). For instance, previous experiments have demonstrated that the firing rate of place fields in the start box of some mazes are predictive of the animal’s final destination (Ainge, Tamosiunaite, et al., 2007; Ferbinteanu & Shapiro, 2003). We sought to understand whether this prospective firing is in fact related to the goal the rat is planning to navigate to or the route the rat is planning to take. Our results provide strong evidence for the latter, suggesting that rats may not be aware of the location of specific goals and may not be aware of their environment in the form of a contiguous map. However, we also found behavioural evidence that rats are aware of specific goal locations, suggesting that place cells in the hippocampus may not be responsible for this representation and that it may reside elsewhere (Hok, Chah, Save, & Poucet, 2013). Unlike their typical activity in an open field, place cells often have multiple place fields in geometrically similar areas of a multicompartment environment (Derdikman et al., 2009; Spiers et al., 2013). For example, Spiers et al. (2013) found that in an environment composed of four parallel compartments, place cells often fired similarly in multiple compartments, despite the active movement of the rat between them. We were able to replicate this phenomenon, furthermore, we were also able to show that if the compartments are arranged in a radial configuration this repetitive firing does not occur as frequently. We suggest that this place field repetition is driven by inputs from Boundary Vector Cells (BVCs) in neighbouring brain regions which are in turn greatly modulated by inputs from the head direction system. This is supported by a novel BVC model of place cell firing which predicts our observed results accurately. If place cells form the neural basis of a cognitive map one would predict spatial learning to be difficult in an environment where repetitive firing is observed frequently (Spiers et al., 2013). We tested this hypothesis by training animals on an odour discrimination task in the maze environments described above. We found that rats trained in the parallel version of the task were significantly impaired when compared to the radial version. These results support the hypothesis that place cells form the neural basis of a cognitive map; in environments where it is difficult to discriminate compartments based on the firing of place cells, rats find it similarly difficult to discriminate these compartments as shown by their behaviour. The experiments reported here are discussed in terms of a cognitive map, the likelihood that such a construct exists and the possibility that place cells form the neural basis of such a representation. Although the results of our experiments could be interpreted as evidence that animals do not possess a cognitive map, ultimately they suggest that animals do have a cognitive map and that place cells form a more than adequate substrate for this representation