Dataset Information

A Closed-Loop Optogenetic Platform.

ABSTRACT: Neuromodulation is an established treatment for numerous neurological conditions, but to expand the therapeutic scope there is a need to improve the spatial, temporal and cell-type specificity of stimulation. Optogenetics is a promising area of current research, enabling optical stimulation of genetically-defined cell types without interfering with concurrent electrical recording for closed-loop control of neural activity. We are developing an open-source system to provide a platform for closed-loop optogenetic neuromodulation, incorporating custom integrated circuitry for recording and stimulation, real-time closed-loop algorithms running on a microcontroller and experimental control via a PC interface. We include commercial components to validate performance, with the ultimate aim of translating this approach to humans. In the meantime our system is flexible and expandable for use in a variety of preclinical neuroscientific applications. The platform consists of a Controlling Abnormal Network Dynamics using Optogenetics (CANDO) Control System (CS) that interfaces with up to four CANDO headstages responsible for electrical recording and optical stimulation through custom CANDO LED optrodes. Control of the hardware, inbuilt algorithms and data acquisition is enabled via the CANDO GUI (Graphical User Interface). Here we describe the design and implementation of this system, and demonstrate how it can be used to modulate neuronal oscillations in vitro and in vivo.

SUBMITTER: Firfilionis D

PROVIDER: S-EPMC8462298 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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A Closed-Loop Optogenetic Platform.

Firfilionis Dimitrios D Hutchings Frances F Tamadoni Reza R Walsh Darren D Turnbull Mark M Escobedo-Cousin Enrique E Bailey Richard G RG Gausden Johannes J Patel Aaliyah A Haci Dorian D Liu Yan Y LeBeau Fiona E N FEN Trevelyan Andrew A Constandinou Timothy G TG O'Neill Anthony A Kaiser Marcus M Degenaar Patrick P Jackson Andrew A

Frontiers in neuroscience 20210910

Neuromodulation is an established treatment for numerous neurological conditions, but to expand the therapeutic scope there is a need to improve the spatial, temporal and cell-type specificity of stimulation. Optogenetics is a promising area of current research, enabling optical stimulation of genetically-defined cell types without interfering with concurrent electrical recording for closed-loop control of neural activity. We are developing an open-source system to provide a platform for closed- ...[more]

PMID: 34566564

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Project description:Targeted interrogation of brain networks through invasive brain stimulation has become an increasingly important research tool as well as therapeutic modality. The majority of work with this emerging capability has been focused on open-loop approaches. Closed-loop techniques, however, could improve neuromodulatory therapies and research investigations by optimizing stimulation approaches using neurally informed, personalized targets. Implementing closed-loop systems is challenging particularly with regard to applying consistent strategies considering inter-individual variability. In particular, during intracranial epilepsy monitoring, where much of this research is currently progressing, electrodes are implanted exclusively for clinical reasons. Thus, detection and stimulation sites must be participant- and task-specific. The system must run in parallel with clinical systems, integrate seamlessly with existing setups, and ensure safety features are in place. In other words, a robust, yet flexible platform is required to perform different tests with a single participant and to comply with clinical requirements. In order to investigate closed-loop stimulation for research and therapeutic use, we developed a Closed-Loop System for Electrical Stimulation (CLoSES) that computes neural features which are then used in a decision algorithm to trigger stimulation in near real-time. To summarize CLoSES, intracranial electroencephalography (iEEG) signals are acquired, band-pass filtered, and local and network features are continuously computed. If target features are detected (e.g. above a preset threshold for a certain duration), stimulation is triggered. Not only could the system trigger stimulation while detecting real-time neural features, but we incorporated a pipeline wherein we used an encoder/decoder model to estimate a hidden cognitive state from the neural features. CLoSES provides a flexible platform to implement a variety of closed-loop experimental paradigms in humans. CLoSES has been successfully used with twelve patients implanted with depth electrodes in the epilepsy monitoring unit. During cognitive tasks (N=5), stimulation in closed loop modified a cognitive hidden state on a trial by trial basis. Sleep spindle oscillations (N=6) and sharp transient epileptic activity (N=9) were detected in near real-time, and stimulation was applied during the event or at specified delays (N=3). In addition, we measured the capabilities of the CLoSES system. Total latency was related to the characteristics of the event being detected, with tens of milliseconds for epileptic activity and hundreds of milliseconds for spindle detection. Stepwise latency, the actual duration of each continuous step, was within the specified fixed-step duration and increased linearly with the number of channels and features. We anticipate that probing neural dynamics and interaction between brain states and stimulation responses with CLoSES will lead to novel insights into the mechanism of normal and pathological brain activity, the discovery and evaluation of potential electrographic biomarkers of neurological and psychiatric disorders, and the development and testing of patient-specific stimulation targets and control signals before implanting a therapeutic device.

Project description:OBJECTIVE:Optogenetics provides a means to probe functional connections between brain areas. By activating a set of presynaptic neurons and recording the activity from a downstream brain area, one can establish the sign and strength of a feedforward connection. One challenge is that there are virtually limitless patterns that can be used to stimulate a presynaptic brain area. Functional influences on downstream brain areas can depend not just on whether presynaptic neurons were activated, but how they were activated. Corticofugal axons from the auditory cortex (ACtx) heavily innervate the auditory tectum, the inferior colliculus (IC). Here, we sought to determine whether different modes of corticocollicular activation could titrate the strength of feedforward modulation of sound processing in IC neurons. APPROACH:We used multi-channel electrophysiology and optogenetics to record from multiple regions of the IC in awake head-fixed mice while optogenetically stimulating ACtx neurons expressing Chronos, an ultra-fast channelrhodopsin. To identify cortical activation patterns associated with the strongest effects on IC firing rates, we employed a closed-loop evolutionary optimization procedure that tailored the voltage command signal sent to the laser based on spike feedback from single IC neurons. MAIN RESULTS:Within minutes, our evolutionary search procedure converged on ACtx stimulation configurations that produced more effective and widespread enhancement of IC unit activity than generic activation parameters. Cortical modulation of midbrain spiking was bi-directional, as the evolutionary search procedure could be programmed to converge on activation patterns that either suppressed or enhanced sound-evoked IC firing rate. SIGNIFICANCE:This study introduces a closed-loop optimization procedure to probe functional connections between brain areas. Our findings demonstrate that the influence of descending feedback projections on subcortical sensory processing can vary both in sign and degree depending on how cortical neurons are activated in time.

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A Closed-Loop Optogenetic Platform.

Publications

A Closed-Loop Optogenetic Platform.

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