Brain-machine interfaces (BMI) were born to control “actions from thoughts” in order to recover motor capability of patients with impaired functional connectivity between the central and peripheral nervous system. The final goal of our studies is the development of a new proof-of-concept BMI—a neuromorphic chip for brain repair—to reproduce the functional organization of a damaged part of the central nervous system. To reach this ambitious goal, we implemented a multidisciplinary “bottom-up” approach in which in vitro networks are the paradigm for the development of an in silico model to be incorporated into a neuromorphic device. In this paper we present the overall strategy and focus on the different building blocks of our studies: (i) the experimental characterization and modeling of “finite size networks” which represent the smallest and most general self-organized circuits capable of generating spontaneous collective dynamics; (ii) the induction of lesions in neuronal networks and the whole brain preparation with special attention on the impact on the functional organization of the circuits; (iii) the first production of a neuromorphic chip able to implement a real-time model of neuronal networks. A dynamical characterization of the finite size circuits with single cell resolution is provided. A neural network model based on Izhikevich neurons was able to replicate the experimental observations. Changes in the dynamics of the neuronal circuits induced by optical and ischemic lesions are presented respectively for in vitro neuronal networks and for a whole brain preparation. Finally the implementation of a neuromorphic chip reproducing the network dynamics in quasi-real time (10 ns precision) is presented.

For Alzheimer’s disease (AD), aging is the main risk factor, but whether cognitive impairments due to aging resemble early AD deficits is not yet defined. When working with mouse models of AD, the situation is just as complicated, because only a few studies track the progression of the disease at different ages, and most ignore how the aging process affects control mice. In this work, we addressed this problem by comparing the aging process of PS2APP (AD) and wild-type (WT) mice at the level of spontaneous brain electrical activity under anesthesia. Using local field potential recordings, obtained with a linear probe that traverses the posterior parietal cortex and the entire hippocampus, we analyzed how multiple electrical parameters are modified by aging in AD and WT mice. With this approach, we highlighted AD specific features that appear in young AD mice prior to plaque deposition or that are delayed at 12 and 16 months of age. Furthermore, we identified aging characteristics present in WT mice but also occurring prematurely in young AD mice. In short, we found that reduction in the relative power of slow oscillations (SO) and Low/High power imbalance are linked to an AD phenotype at its onset. The loss of SO connectivity and cortico-hippocampal coupling between SO and higher frequencies as well as the increase in UP-state and burst durations are found in young AD and old WT mice. We show evidence that the aging process is accelerated by the mutant PS2 itself and discuss such changes in relation to amyloidosis and gliosis.

Numerous experiments require low latencies in the detection and processing of the neural brain activity to be feasible, in the order of a few milliseconds from action to reaction. In this paper, a design for sub-millisecond detection and communication of the spiking activity detected by an array of 32 intracortical microelectrodes is presented, exploiting the real-time processing provided by Field Programmable Gate Array (FPGA). The design is embedded in the commercially available RHS stimulation/recording controller from Intan Technologies, that allows recording intracortical signals and performing IntraCortical MicroStimulation (ICMS). The Spike Detector (SD) is based on the Smoothed Nonlinear Energy Operator (SNEO) and includes a novel approach to estimate an RMS-based firing-rate-independent threshold, that can be tuned to fine detect both the single Action Potential (AP) and Multi Unit Activity (MUA). A low-latency SD together with the ICMS capability, creates a powerful tool for Brain-Computer-Interface (BCI) closed-loop experiments relying on the neuronal activity-dependent stimulation. The design also includes: A third order Butterworth high-pass IIR filter and a Savitzky-Golay polynomial fitting; a privileged fast USB connection to stream the detected spikes to a host computer and a sub-milliseconds latency Universal Asynchronous Receiver-Transmitter (UART) protocol communication to send detections and receive ICMS triggers. The source code and the instruction of the project can be found on GitHub.