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EoE Sub Articles

All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.
1. Surgery
NOTE: The exact details of the surgery for closed-loop stimulation depend on the type of recording probes used and the brain areas targeted. In most cases, however, a typical surgery will consist of the following steps.
<ol>
	<li>Bring a cage with a rat to the surgery room to b...

triggering a closed-loop stimulation by neuron spiking activity

Source: Molina, L. et al. <a href="https://app.jove.com/v/59812">Using Neuron Spiking Activity to Trigger Closed-Loop Stimuli in Neurophysiological Experiments.</a> J. Vis. Exp. (2019).
This video demonstrates the operation of closed-loop stimulation in a rat with a surgically implanted device to record neural activity. Neuronal signals are first recorded and analyzed. Template waveforms are then uploaded, and parameters are defined to trigger closed-loop stimulation.

Triggering a Closed-Loop Stimulation by Neuron Spiking Activity

All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.
1. ...

Take a rat with a surgically implanted device to record neural activity.
Download all the required software.
Record the initial spiking data and select template waveforms.
Resume data recording for the closed-loop stimulation experiment.
Closed-loop stimulation is a system in which sensors continuously record neural signals.
Upon detecting specific neural activity, a predefined stimulation is generated as feedback.
The sensors then record the neural response to this stimulation, continuing the loop.
Run the required program.
Load template waveforms from the initial recordings and select the desired number of templates required to trigger the stimulation.
Define a minimal number of neurons needed to initiate the stimulation.
Set parameters for the time period during which spike signals detected from different neurons will be considered co-active.
Begin the closed-loop experiment with predefined stimulation.

triggering-a-closed-loop-stimulation-by-neuron-spiking-activity

Research

JoVE Encyclopedia of Experiments

Neuroscience

Neurophysiology

Stimulation and Modulation Techniques

Real-time Electrophysiology: Using Closed-loop Protocols to Probe Neuronal Dynamics and Beyond

Experimental neuroscience is witnessing an increased interest in the development and application of novel and often complex, closed-loop protocols, where the stimulus applied depends in real-time on the response of the system. Recent applications range from the implementation of virtual reality systems for studying motor responses both in mice1 and in zebrafish2, to control of seizures following cortical stroke using optogenetics3. A key advantage of closed-loop techniques resides in the capability of probing higher dimensional properties that are not directly accessible or that depend on multiple variables, such as neuronal excitability4 and reliability, while at the same time maximizing the experimental throughput. In this contribution and in the context of cellular electrophysiology, we describe how to apply a variety of closed-loop protocols to the study of the response properties of pyramidal cortical neurons, recorded intracellularly with the patch clamp technique in acute brain slices from the somatosensory cortex of juvenile rats. As no commercially available or open source software provides all the features required for efficiently performing the experiments described here, a new software toolbox called LCG5 was developed, whose modular structure maximizes reuse of computer code and facilitates the implementation of novel experimental paradigms. Stimulation waveforms are specified using a compact meta-description and full experimental protocols are described in text-based configuration files. Additionally, LCG has a command-line interface that is suited for repetition of trials and automation of experimental protocols.

Closed-loop protocols are becoming increasingly widespread in modern day electrophysiology. We present a simple, versatile and inexpensive way to perform complex electrophysiological protocols in cortical pyramidal neurons in vitro, using a desktop computer and a digital acquisition board.

Experimental neuroscience is witnessing an increased interest in the development and application of novel and often complex, closed-loop protocols, where ...

JoVE Journal

Deep Brain Stimulation for Treatment of Major Depression

Closed-Loop Neurostimulation for Biomarker-Driven, Personalized Treatment of Major Depressive Disorder

Deep brain stimulation involves the administration of electrical stimulation to targeted brain regions for therapeutic benefit. In the context of major depressive disorder (MDD), most studies to date have administered continuous or open-loop stimulation with promising but mixed results. One factor contributing to these mixed results may stem from when the stimulation is applied. Stimulation administration specific to high-symptom states in a personalized and responsive manner may be more effective at reducing symptoms compared to continuous stimulation and may avoid diminished therapeutic effects related to habituation. Additionally, a lower total duration of stimulation per day is advantageous for reducing device energy consumption. This protocol describes an experimental workflow using a chronically implanted neurostimulation device to achieve closed-loop stimulation for individuals with treatment-refractory MDD. This paradigm hinges on determining a patient-specific neural biomarker that is related to states of high symptoms and programming the device detectors, such that stimulation is triggered by this read-out of symptom state. The described procedures include how to obtain neural recordings concurrent with patient symptom reports, how to use these data in a state-space model approach to differentiate low- and high-symptom states and corresponding neural features, and how to subsequently program and tune the device to deliver closed-loop stimulation therapy.

Author Spotlight: Therapeutic Benefit of Closed-Loop Deep Brain Stimulation in Depression Treatment 

Deep brain stimulation triggered by a patient-specific neural biomarker of a high-symptom state may better control symptoms of major depressive disorder compared to continuous, open-loop stimulation. This protocol provides a workflow for identifying a patient-specific neural biomarker and controlling the delivery of therapeutic stimulation based on the identified biomarker.

Deep brain stimulation involves the administration of electrical stimulation to targeted brain regions for therapeutic benefit. In the context of major ...

Programming Device Detector Settings for Closed-Loop Neurostimulation

Begin by logging onto the patient Data Management System, using the programmer. Next, select the correct Patient, Programming, and Change Detection. Based on the selected personalized biomarker, select the correct channel for detecting the activity.For activity detection, select Rhythmic Activity, which connotes a band pass detector. Click More Controls in Advanced Settings. Select the desired minimum and maximum frequency.Ensure to turn on the band pass and turn off the line length in Area Settings. Additionally, set the inversion logic to Not Inverted. Program the detector by setting the minimum amplitude to 0.8%and the minimum duration to 0.64 seconds.After selecting all the detector settings, click the Done button to close all programming windows. Place the wand over the patient's implantable neurostimulator, and select Review All Changes in Program RNS. The biomarker discovery of symptoms was performed based on the neurospectral power between the low depression and the high depression states.It was found that the best choice for a frequency-specific biomarker in this example is 13 to 30 hertz of OFC, three to four.

Triggering a Closed-Loop Stimulation by Neuron Spiking Activity

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