A Multiple-Plasticity Spiking Neural Network Embedded in a Closed-Loop Control System to Model Cerebellar Pathologies

The cerebellum plays a crucial role in sensorimotor control and cerebellar disorders compromise adaptation and learning of motor responses. However, the link between alterations at network level and cerebellar dysfunction is still unclear. In principle, this understanding would benefit of the development of an artificial system embedding the salient neuronal and plastic properties of the cerebellum and operating in closed-loop. To this aim, we have exploited a realistic spiking computational model of the cerebellum to analyze the network correlates of cerebellar impairment. The model was modified to reproduce three different damages of the cerebellar cortex: (i) a loss of the main output neurons (Purkinje Cells), (ii) a lesion to the main cerebellar afferents (Mossy Fibers), and (iii) a damage to a major mechanism of synaptic plasticity (Long Term Depression). The modified network models were challenged with an Eye-Blink Classical Conditioning test, a standard learning paradigm used to evaluate cerebellar impairment, in which the outcome was compared to reference results obtained in human or animal experiments. In all cases, the model reproduced the partial and delayed conditioning typical of the pathologies, indicating that an intact cerebellar cortex functionality is required to accelerate learning by transferring acquired information to the cerebellar nuclei. Interestingly, depending on the type of lesion, the redistribution of synaptic plasticity and response timing varied greatly generating specific adaptation patterns. Thus, not only the present work extends the generalization capabilities of the cerebellar spiking model to pathological cases, but also predicts how changes at the neuronal level are distributed across the network, making it usable to infer cerebellar circuit alterations occurring in cerebellar pathologies

A realistic morpho-anatomical connection strategy for modelling full-scale point-neuron microcircuits

The modeling of extended microcircuits is emerging as an effective tool to simulate the neurophysiological correlates of brain activity and to investigate brain dysfunctions. However, for specific networks, a realistic modeling approach based on the combination of available physiological, morphological and anatomical data is still an open issue. One of the main problems in the generation of realistic networks lies in the strategy adopted to build network connectivity. Here we propose a method to implement a neuronal network at single cell resolution by using the geometrical probability volumes associated with pre- and postsynaptic neurites. This allows us to build a network with plausible connectivity properties without the explicit use of computationally intensive touch detection algorithms using full 3D neuron reconstructions. The method has been benchmarked for the mouse hippocampus CA1 area, and the results show that this approach is able to generate full-scale brain networks at single cell resolution that are in good agreement with experimental findings. This geometric reconstruction of axonal and dendritic occupancy, by effectively reflecting morphological and anatomical constraints, could be integrated into structured simulators generating entire circuits of different brain areas facilitating the simulation of different brain regions with realistic models

Applications of Robotics for Autism Spectrum Disorder: a Scoping Review

Robotic therapies are receiving growing interest in the autism field, especially for the improvement of social skills of children, enhancing traditional human interventions. In this work, we conduct a scoping review of the literature in robotics for autism, providing the largest review on this field from the last five years. Our work underlines the need to better characterize participants and to increase the sample size. It is also important to develop homogeneous training protocols to analyse and compare the results. Nevertheless, 7 out of the 10 Randomized control trials reported a significant impact of robotic therapy. Overall, robot autonomy, adaptability and personalization as well as more standardized outcome measures were pointed as the most critical issues to address in future research

A multi-layer mean-field model of the cerebellum embedding microstructure and population-specific dynamics

Mean-field (MF) models are computational formalism used to summarize in a few statistical parameters the salient biophysical properties of an inter-wired neuronal network. Their formalism normally incorporates different types of neurons and synapses along with their topological organization. MFs are crucial to efficiently implement the computational modules of large-scale models of brain function, maintaining the specificity of local cortical microcircuits. While MFs have been generated for the isocortex, they are still missing for other parts of the brain. Here we have designed and simulated a multi-layer MF of the cerebellar microcircuit (including Granule Cells, Golgi Cells, Molecular Layer Interneurons, and Purkinje Cells) and validated it against experimental data and the corresponding spiking neural network (SNN) microcircuit model. The cerebellar MF was built using a system of equations, where properties of neuronal populations and topological parameters are embedded in inter-dependent transfer functions. The model time constant was optimised using local field potentials recorded experimentally from acute mouse cerebellar slices as a template. The MF reproduced the average dynamics of different neuronal populations in response to various input patterns and predicted the modulation of the Purkinje Cells firing depending on cortical plasticity, which drives learning in associative tasks, and the level of feedforward inhibition. The cerebellar MF provides a computationally efficient tool for future investigations of the causal relationship between microscopic neuronal properties and ensemble brain activity in virtual brain models addressing both physiological and pathological conditions

Complex dynamics in simplified neuronal models: reproducing Golgi cell electroresponsiveness

Brain neurons exhibit complex electroresponsive properties – including intrinsic subthreshold oscillations and pacemaking, resonance and phase-reset – which are thought to play a critical role in controlling neural network dynamics. Although these properties emerge from detailed representations of molecular-level mechanisms in “realistic” models, they cannot usually be generated by simplified neuronal models (although these may show spike-frequency adaptation and bursting). We report here that this whole set of properties can be generated by the extended generalized leaky integrate-and-fire (E-GLIF) neuron model. E-GLIF derives from the GLIF model family and is therefore mono-compartmental, keeps the limited computational load typical of a linear low-dimensional system, admits analytical solutions and can be tuned through gradient-descent algorithms. Importantly, E-GLIF is designed to maintain a correspondence between model parameters and neuronal membrane mechanisms through a minimum set of equations. In order to test its potential, E-GLIF was used to model a specific neuron showing rich and complex electroresponsiveness, the cerebellar Golgi cell, and was validated against experimental electrophysiological data recorded from Golgi cells in acute cerebellar slices. During simulations, E-GLIF was activated by stimulus patterns, including current steps and synaptic inputs, identical to those used for the experiments. The results demonstrate that E-GLIF can reproduce the whole set of complex neuronal dynamics typical of these neurons – including intensity-frequency curves, spike-frequency adaptation, post-inhibitory rebound bursting, spontaneous subthreshold oscillations, resonance, and phase-reset – providing a new effective tool to investigate brain dynamics in large-scale simulations

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Response Dynamics in an Olivocerebellar Spiking Neural Network With Non-linear Neuron Properties

Sensorimotor signals are integrated and processed by the cerebellar circuit to predict accurate control of actions. In order to investigate how single neuron dynamics and geometrical modular connectivity affect cerebellar processing, we have built an olivocerebellar Spiking Neural Network (SNN) based on a novel simplification algorithm for single point models (Extended Generalized Leaky Integrate and Fire, EGLIF) capturing essential non-linear neuronal dynamics (e.g., pacemaking, bursting, adaptation, oscillation and resonance). EGLIF models specifically tuned for each neuron type were embedded into an olivocerebellar scaffold reproducing realistic spatial organization and physiological convergence and divergence ratios of connections. In order to emulate the circuit involved in an eye blink response to two associated stimuli, we modeled two adjacent olivocerebellar microcomplexes with a common mossy fiber input but different climbing fiber inputs (either on or off). EGLIF-SNN model simulations revealed the emergence of fundamental response properties in Purkinje cells (burst-pause) and deep nuclei cells (pause-burst) similar to those reported in vivo. The expression of these properties depended on the specific activation of climbing fibers in the microcomplexes and did not emerge with scaffold models using simplified point neurons. This result supports the importance of embedding SNNs with realistic neuronal dynamics and appropriate connectivity and anticipates the scale-up of EGLIF-SNN and the embedding of plasticity rules required to investigate cerebellar functioning at multiple scales

Spiking Cerebellar Model with Damaged Cortical Neural Population Reproduces Human Ataxic Behaviors in Perturbed Upper Limb Reaching

The fundamental role of the cerebellum in motor learning explains the deficits of cerebellar patients in adaptation to a changing environment. For example, lesions to the cerebellar cortex compromise performance during tasks like reaching a target under a force field perturbation. However, the exact relationship between neural damages and misbehaviors still needs to be clarified. To this aim, it could become a turning point to exploit a bio-inspired cerebellar model able to simulate multiple tasks in closed-loop, under physiological and different pathological conditions. In the present study, we used a well-established Spiking Neural Network representing a cerebellar microcomplex to reproduce alterations in a perturbed reaching task, after lesions to the neural population in the cerebellar cortex. Following a multiscale approach, we explored different amounts of damage and analyzed the modified behavior, matching the results of a literature reference study. Then, we could make predictions about the underlying altered neural activity, showing the neural causes of high-level impairments. The results demonstrate the generalization capabilities of the model, extending previous studies on different lesions and tasks. We showed the strong potentialities of computational neuroscience in investigating cerebellar diseases through a non-invasive approach, allowing to isolate damages, test multiple configurations, and suggest treatments thanks to a deeper understanding of pathologie