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Register a new userA System-on-Chip for Closed-loop Optogenetic Sleep Modulation
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Stimulation of target neuronal populations using optogenetic techniques during specific sleep stages has begun to elucidate the mechanisms and effects of sleep. To conduct closed-loop optogenetic sleep studies in untethered animals, we designed a fully integrated, low-power system-on-chip (SoC) for real-time sleep stage classification and stage-specific optical stimulation. The SoC consists of a 4-channel analog front-end for recording polysomnography signals, a mixed-signal machine-learning (ML) core, and a 16-channel optical stimulation back-end. A novel ML algorithm and innovative circuit design techniques improved the online classification performance while minimizing power consumption. The SoC was designed and simulated in 180 nm CMOS technology. In an evaluation using an expert labeled sleep database with 20 subjects, the SoC achieves a high sensitivity of 0.806 and a specificity of 0.947 in discriminating 5 sleep stages. Overall power consumption in continuous operation is 97 uW.
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We present a high-throughput optogenetic illumination system capable of simultaneous closed-loop light delivery to specified targets in populations of moving Caenorhabditis elegans. The instrument addresses three technical challenges: it delivers targeted illumination to specified regions of the animals body such as its head or tail; it automatically delivers stimuli triggered upon the animals behavior; and it achieves high throughput by targeting many animals simultaneously. The instrument was used to optogenetically probe the animals behavioral response to competing mechanosensory stimuli in the the anterior and posterior soft touch receptor neurons. Responses to more than $10^4$ stimulus events from a range of anterior-posterior intensity combinations were measured. The animals probability of sprinting forward in response to a mechanosensory stimulus depended on both the anterior and posterior stimulation intensity, while the probability of reversing depended primarily on the posterior stimulation intensity. We also probed the animals response to mechanosensory stimulation during the onset of turning, a relatively rare behavioral event, by delivering stimuli automatically when the animal began to turn. Using this closed-loop approach, over $10^3$ stimulus events were delivered during turning onset at a rate of 9.2 events per worm-hour, a greater than 25-fold increase in throughput compared to previous investigations. These measurements validate with greater statistical power previous findings that turning acts to gate mechanosensory evoked reversals. Compared to previous approaches, the current system offers targeted optogenetic stimulation to specific body regions or behaviors with many-fold increases in throughput to better constrain quantitative models of sensorimotor processing.
Sensory feedback is critical to the performance of neural prostheses that restore movement control after neurological injury. Recent advances in direct neural control of paralyzed arms present new requirements for miniaturized, low-power sensor systems. To address this challenge, we developed a fully-integrated wireless sensor-brain-machine interface (SBMI) system for communicating key somatosensory signals, fingertip forces and limb joint angles, to the brain. The system consists of a tactile force sensor, an electrogoniometer, and a neural interface. The tactile force sensor features a novel optical waveguide on CMOS design for sensing. The electrogoniometer integrates an ultra low-power digital signal processor (DSP) for real-time joint angle measurement. The neural interface enables bidirectional neural stimulation and recording. Innovative designs of sensors and sensing interfaces, analog-to-digital converters (ADC) and ultra wide-band (UWB) wireless transceivers have been developed. The prototypes have been fabricated in 180nm standard CMOS technology and tested on the bench and in vivo. The developed system provides a novel solution for providing somatosensory feedback to next-generation neural prostheses.
Modern network-on-chip (NoC) systems face reliability issues due to process and environmental variations. The power supply noise (PSN) in the power delivery network of a NoC plays a key role in determining reliability. PSN leads to voltage droop, which can cause timing errors in the NoC. This paper makes a novel contribution towards formally analyzing PSN in NoC systems. We present a probabilistic model checking approach to observe the PSN in a generic 2x2 mesh NoC with a uniform random traffic load. Key features of PSN are measured at the behavioral level. To tackle state explosion, we apply incremental abstraction techniques, including a novel probabilistic choice abstraction, based on observations of NoC behavior. The Modest Toolset is used for probabilistic modeling and verification. Results are obtained for several flit injection patterns to reveal their impacts on PSN. Our analysis finds an optimal flit pattern generation with zero probability of PSN events and suggests spreading flits rather than releasing them in consecutive cycles in order to minimize PSN.
This paper is concerned with a bilinear control problem for enhancing convection-cooling via an incompressible velocity field. Both optimal open-loop control and closed-loop feedback control designs are addressed. First and second order optimality conditions for characterizing the optimal solution are discussed. In particular, the method of instantaneous control is applied to establish the feedback laws. Moreover, the construction of feedback laws is also investigated by directly utilizing the optimality system with appropriate numerical discretization schemes. Computationally, it is much easier to implement the closed-loop feedback control than the optimal open-loop control, as the latter requires to solve the state equations forward in time, coupled with the adjoint equations backward in time together with a nonlinear optimality condition. Rigorous analysis and numerical experiments are presented to demonstrate our ideas and validate the efficacy of the control designs.
The majority of inherited retinal degenerations are due to photoreceptor cell death. In many cases ganglion cells are spared making it possible to stimulate them to restore visual function. Several studies (Bi et al., 2006; Lin et al., 2008; Sengupta et al., 2016; Caporale et al., 2011; Berry et al., 2017) have shown that it is possible to express an optogenetic protein in ganglion cells and make them light sensitive. This is a promising strategy to restore vision since optical targeting may be more precise than electrical stimulation with a retinal prothesis. However the spatial resolution of optogenetically-reactivated retinas has not been measured with fine-grained stimulation patterns. Since the optogenetic protein is also expressed in axons, it is unclear if these neurons will only be sensitive to the stimulation of a small region covering their somas and dendrites, or if they will also respond to any stimulation overlapping with their axon, dramatically impairing spatial resolution. Here we recorded responses of mouse and macaque retinas to random checkerboard patterns following an in vivo optogenetic therapy. We show that optogenetically activated ganglion cells are each sensitive to a small region of visual space. A simple model based on this small receptive field predicted accurately their responses to complex stimuli. From this model, we simulated how the entire population of light sensitive ganglion cells would respond to letters of different sizes. We then estimated the maximal acuity expected by a patient, assuming it could make an optimal use of the information delivered by this reactivated retina. The obtained acuity is above the limit of legal blindness. This high spatial resolution is a promising result for future clinical studies.
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