Name: Deep Brain Stimulation with Simultaneous fMRI in Rodents (Video) | JoVE Journal
Uploaded: 2014-02-15T14:00:00.000+00:00
Duration: 11 min 9 s
Description: Learn deep brain stimulation with simultaneous fMRI in rodents to map brain responses across multiple targets. This method enables real-time analysis of functional connectivity and neural activity patterns.

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5 minutes

We thank Shaili Jha and Heather Decot for assistance with filming.

Ethics Statement: This procedure is in accordance with the National Institutes of Health Guidelines for Animal Research (Guide for the Care and Use of Laboratory Animals) and is approved by the University of North Carolina Institutional Animal Care and Use Committee.
1. Electrode Implantation
The first step is electrode implantation. In this step, an electrode is unilaterally implanted into the subthalamic nucleus (STN), a small nucleus with translational significance for Parkinson&#8217;s disease treatment using the following methods:
<ol>
	<li>Sterilize all surgical equipment using an autoclave, or antiseptic solution where autoclaving is not possible (e.g.&#160;for electrode sterility). Note: this is a short-term survival surgery, and thus aseptic technique is essential. Following surgery, animals can be imaged after a brief recovery period (48 hr) or up to several weeks later.</li>
	<li>Anesthetize the rat (Adult Sprague-Dawley rats 250-400 g) using 2.5% isoflurane administered via endotracheal intubation and a small animal ventilator. Fix the rat to a stereotactic surgical frame and prepare the surgical site using aseptic techniques.</li>
	<li>Prepare and ensure that the electrode is sterile. A homemade 2-channel tungsten microwire electrode is used for this procedure, though many MRI-compatible electrode types will work. The electrode type used may affect the area of tissue mechanically damaged by the procedure, the area of tissue stimulated, and the accuracy of implantation, thus affecting the overall experimental result. If the electrode type is not able to be autoclaved, use povidone-iodine antiseptic to sterilize the electrode as far as is possible.</li>
	<li>Using scissors remove the scalp over the site of implantation with a diameter of approximately 1.5 cm, to uncover bregma and lambda on the skull. Remove the muscle and fascia overlying the skull and stop all bleeding using electrocautery.</li>
	<li>Scratch the skull surface in multiple directions with a scalpel to improve dental cement adhesion (step 1.8). Level Bregma and Lambda in the horizontal direction.</li>
	<li>To target STN, at 3.6 mm posterior to Bregma and 2.5 mm lateral to midline, use a small-tipped electric drill to create a burr hole measuring approximately 1.5 mm in diameter. Note: The exact location of the STN in reference to stereotaxic coordinates may vary by rat strain, weight, and gender. Adult rats of the same gender should be used to minimize any variation in location. If possible, pre-operational anatomical scans or intraoperative electrical recordings should be used to identify the STN location on an individual subject basis. Further, electrode termination sites should be histologically verified to ensure target accuracy.
	<ol>
		<li>Carefully make an incision in the dura, and use small blunt forceps to move the dura to the sides of the hole. Stop any bleeding using sterile cotton soaked in saline. Create holes for one&#160;or more MR-compatible screws) and insert them gently in the skull until they are stable. Screws may be placed in any location where they will not disrupt the placement of the external connector for the DBS electrode (e.g.&#160;not directly behind the STN ipsilateral to the electrode). We recommend placements at the lateral edges of the skull, ideally directly posterior to the lambda suture. At this point, the skull is relatively thick, reducing the likelihood that screws will damage the cortex.&#8221; Note: Brass screws cut to 4-5 mm in length are used in this protocol, although plastic screws are also suitable.</li>
	</ol>
	</li>
	<li>Place the electrode on the stereotactic arm, ensuring that it is straight and vertical. Touch the electrode to Bregma, then move the electrode exactly 3.6 mm posterior to Bregma and 2.5 mm lateral to midline and touch the cortical surface with the electrode. From the cortical surface, insert the electrode 7.8 mm ventrally. These coordinates are determined by reference to a neuroanatomical atlas1.</li>
	<li>Place a layer of dental cement over the skull including the skull screws and electrode insertion point. Wait until the cement is completely hardened prior to removing the electrode from the stereotactic frame. Bend the electrode backward and use additional cement to cover the rest of the electrode tract and connector for durability.</li>
</ol>
2. fMRI Preparation
The second step is the setup for fMRI, including positioning of the coil and setup of physiological monitoring equipment.
<ol>
	<li>Secure the animal&#8217;s head to prevent motion during the scan. Note: A custom plastic intraauricular bar system is used here for head fixation. Place the bars into the ear canals and secure to the headpiece so that the head rotates smoothly in the vertical direction with no horizontal rotation. Secure the head position by fixing the upper teeth to the apparatus.</li>
	<li>Anesthetize the rat completely and monitor end tidal CO2 to ensure stability throughout all scans. To maintain anesthesia, ventilation and control end tidal CO2 levels during the scan, an MR-compatible small animal ventilation system combined with an isoflurane vaporizer is used here, though a variety of anesthetic and sedation agents may be used in a similar fashion. Set the ventilator to 45 breaths/min with a moderate volume, approximately 500 ml/min of air as a starting volume. Set the isoflurane to 2% and transfer the rat into the scan room. Attach the ventilator&#8217;s output to the rat&#8217;s endotracheal tube and press firmly to secure. Capnometry should be acquired using a tube connected as closely to the endotracheal tube connector as possible. Adjust ventilation volume to produce an end-tidal CO2 of 2.6% to 3.3%.</li>
	<li>Use an MR-compatible small animal holder to insert the rat into the scanner with a circulating hot water bath for temperature control. Tape the pad of the bath onto the holder and cover it with clean absorbent paper. Place the rat onto the hot water bed.</li>
	<li>Monitoring of temperature and carbon dioxide levels are essential to BOLD fMRI, while arterial oxygen saturation and heart rate are also useful physiological parameters. Insert an MR-compatible rectal temperature probe and tape it to the base of the tail, and then adjust the temperature of the water bath to maintain normal body temperature at 37&#160;&#176;C. Monitor arterial oxygen saturation and heart rate using a small animal pulse oximetry system, maintaining them at 95-98% and 250-350 bpm, respectively, which may vary depending on the type of anesthetics used. Oxygen saturation and heart rate are both influenced by depth of anesthesia, ventilation volume and ventilation rate. Ventilation volume and rate may need to be carefully balanced to maintain adequate end-tidal CO2 levels and adequate oxygen saturation.</li>
	<li>A surface coil is needed for BOLD fMRI acquisition. Place the surface coil as close to the surface of the head as possible. Once secured, place toothpaste on the surface of the head on the cement cap in order to reduce susceptibility artifacts near the brain surface. Note: We use a homemade transceiver surface coil with an internal diameter of approximately 1.6 cm, though larger surface coils may be used to optimize the BOLD response in deeper subcortical regions.</li>
	<li>Connect the stimulating electrode to a programmable electrical stimulator system. Note: We use a custom-made programmable TTL triggering system connected to a bipolar stimulator to deliver electrical pulses synchronized to the RF excitations from the MR scans.</li>
	<li>For sedation and paralysis during fMRI data acquisition, use a cocktail of dexmedetomidine (0.1 mg/kg/hr, i.p.) and pancuronium (1 mg/kg/hr, i.p.), combined with low dose isoflurane at 0.5% to prevent epileptic activity2. For drug infusion, an MR-compatible syringe pump must be used if the pump is to be placed in the magnetic environment. Alternatively, a noncompatible pump may be placed outside the magnetic environment provided that extended catheter tubing is used.</li>
</ol>
3. fMRI Data Acquistion
The third step is fMRI acquisition, including positioning, shimming, anatomical scans, and functional scans. A 9.4 Tesla system with a homemade surface coil is used here, though this technique may be adapted to other high-field systems and commercially made MRI coils.
<ol>
	<li>Insert the rat into the scanner and position in the center of the magnet. Use a three-plane scout image to precisely center the rat within the magnet with respect to the brain regions of interest, and FASTMAP shimming to homogenize the magnetic field at the regions of interest.</li>
	<li>Use a sagittal T2-weighted RARE sequence (FOV, 2.56 x 2.56 cm2; matrix size, 256 x 256; slice thickness, 1.5 mm; TR/TE, 1500/11 ms; RARE Factor, 8; Flip Angle, 180&#176;) to find the location of the anterior commissure, and align the subsequent images to this location. Align eight-slice single-shot GE-EPI scans (FOV, 2.56 x 2.56 cm2; matrix size, 96 x 96, reconstructed to 128 x 128; slice thickness, 1mm; TR/TE, 1000/14 ms) to this point with coronal orientation.</li>
	<li>For functional scans, use 70 consecutive EPI scans with 1 second temporal resolution synchronized to the stimulation output, set to 20 sec rest, 10 sec stimulation, followed by 40 sec rest. Allow a minimum of 90 sec between scans to allow for neurovascular recovery. Acquire multiple repeated scans at each stimulation parameter to improve the signal-to-noise ratio by averaging. Use a series of dummy scans (typically 4-8) immediately prior to scanning for noise reduction. Confirm the BOLD response at the time of image acquisition to ensure success of the experiment using the method described in section 4, though averaging, coregistration and skull-stripping may be skipped in this setting.</li>
	<li>After functional scanning is complete, use a T2-weighted RARE spin-echo sequence (FOV, 2.56 x 2.56 cm2; matrix size, 256 x 256; slice thickness, 1 mm; TR/TE, 2500/33 ms; averages, 8) to measure the anatomical position of the electrode in vivo. Acquire multiple coronal and sagittal sections to measure the tip of the electrode artifact along anterior/posterior, medial/lateral and dorsal/ventral axes and confirm electrode placement. High resolution magnetic resonance microscopy (FOV, 1.8 x 1.28 cm; matrix size, 360 x 256; slice thickness, 0.5 mm; TR/TE, 2500/12.6 ms; RARE factor, 8; averages, 280) may be used to examine the precise location of the electrode tract after removal with respect to nearby neuroanatomical structures and confirm the accuracy of electrode placement3.</li>
</ol>
4. fMRI Data Processing and Analysis
The fourth step is processing and analysis of fMRI data, including generation of response maps and calculation of percent BOLD signal change. Custom programs running within a computing environment (e.g.&#160;MATLAB) or commercial fMRI software tools (e.g.&#160;SPM, FSL, or AFNI) may be employed.
<ol>
	<li>Begin with image coregistration and averaging of data first within-subject by frequency, followed by across-subject. Note: We accomplish this using SPM codes.</li>
	<li>Perform skull stripping to remove nonbrain tissue using manually defined region of interest (ROI) with signal thresholding. Automatic skull stripping algorithms may be employed.</li>
	<li>Compile response maps by calculating the correlation coefficient of the relationship between BOLD response over time and the stimulation paradigm for each voxel. Delaying the paradigm several seconds to account for delay in hemodynamic response may be necessary. Set significant level at P &#60; 0.05 after Bonferroni correction. Other statistical methods may be employed. Correcting for multiple comparisons using Random Field Theory or cluster-level correction based on Gaussian Random Field may be performed in place of the Bonferroni correction for more sensitive analysis4. Note: The hemodynamic delay may vary based on brain regions targeted, pharmacologic agents used, and physiological parameters. It is crucial to control these parameters in order to prevent variability within-subject and between-subjects.</li>
	<li>Quantify the BOLD response by defining a ROI to extract time-course data. Average the percent signal change across all voxels within the same anatomical structure. Voxel-wise analysis using the General Linear Model may also be used5.</li>
</ol>

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</ol>

The authors have nothing to disclose.

Simultaneous DBS and fMRI represents a promising experimental toolkit for the identification and characterization of global downstream responses to neural circuit stimulation, in vivo.&#160;The major advantage of this technique over other available tools, such as electrophysiological recordings, lies in the relatively unbiased nature of fMRI, whereby a large and diverse area of brain tissue can be examined for responsiveness to DBS at any target. Although the described protocol is specific for DBS-fMRI in the ra...

Determining the global downstream effects of neural circuit activity represents a major challenge and goal for many areas of systems neuroscience. A paucity of tools are currently available that meet this need, and thus there is a demand for increased accessibility of the appropriate experimental setups.&#160;One such method for evaluating the global consequence of neural circuit activation relies on the simultaneous application of deep brain electrical stimulation (DBS) and functional MRI (fMRI). DBS-fMRI allows for the detection of downstream responses to circuit activation on a large spatial scale, and can be applied at virtually any stimulation target. This toolset is highly suitable for translational preclinical studies, including the characterization of responses to therapeutic high frequency stimulation.
In addition to access to a suitable MRI scanner, successful DBS-fMRI experiments require consideration of a number of variables, including electrode type, sedation method, and maintenance of physiological parameters.&#160;For example, electrode choice should be based on factors relating to stimulation efficacy (e.g.&#160;lead size and conductance, mono- vs. bipolar), as well as MR compatibility and electrode artifact size. Electrode artifacts vary according to electrode material and size, as well as the scan sequence used; thorough pre-experimental testing should be employed to determine the appropriate electrode type for each study. In general, tungsten microwire electrodes are recommended for this protocol. Choice of paralytic and sedative should be made to effectively immobilize the animal and reduce the suppressive effects of certain sedatives on blood-oxygen-level-dependent (BOLD) signal.&#160;Lastly, it is critical to maintain the animal at optimal physiological parameters, including body temperature and oxygen saturation.
The protocol that we have developed for DBS-fMRI overcomes many of these potential obstacles, and in our hands, provides robust and consistent results.&#160;Additionally, these experimental procedures may be readily adopted for the combination of fMRI with alternative stimulation methods, including optogenetic stimulation.&#160;

<table><tbody><tr><td>Isoflurane (Forane)</td><td>Baxter</td><td>1001936060</td><td></td></tr><tr><td>Dexmedetomidine (Dexdomitor)</td><td>Pfizer</td><td>145108-58-3</td><td></td></tr><tr><td>Pancuronium Bromide</td><td>Selleckchem</td><td>S2497</td><td></td></tr><tr><td>9.4 T Small Animal MRI</td><td>Bruker</td><td></td><td>BioSpec System with BGA-9S gradient</td></tr><tr><td>Sterotactic Frame</td><td>Kopf</td><td></td><td>Model 962</td></tr><tr><td>Small Animal Ventilator</td><td>CWE, Inc.</td><td>12-02100</td><td>Model SAR-830</td></tr><tr><td>Dental Cement</td><td>A-M Systems</td><td>525000</td><td>Teets Cold Curing</td></tr><tr><td>MouseOx Plus System</td><td>STARR Life Science Corp.</td><td></td><td></td></tr><tr><td>Capnometer</td><td>Surgivet, Smith Medical</td><td></td><td>V9004 Series</td></tr><tr><td>Stimulus Isolator</td><td>World Precision Instruments</td><td></td><td>Model A365</td></tr><tr><td>MR-compatible Brass Screws</td><td>McMaster Carr</td><td>94070A031</td><td>0-80 thread size, 1/4 in. Can be cut to desired length.</td></tr><tr><td>Tungsten Wire</td><td>California Fine Wire Company</td><td>100211</td><td>Used to construct MR-compatible stimulating microelectrode</td></tr><tr><td>Syringe Pump</td><td>Harvard Appartus</td><td></td><td>Model PHD 2000 (not MRI-compatible)</td></tr></tbody></table>

deep brain stimulation with simultaneous fmri in rodents

Deep Brain Stimulation with Simultaneous fMRI in Rodents

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to image rodents with simultaneous DBS. DBS fMRI presents a number of technical challenges, including accuracy of electrode implantation, MR artifacts created by the electrode, choice of anesthesia and paralytic to minimize any neuronal effects while simultaneously eliminating animal motion, and maintenance of physiological parameters, deviation from which can confound the BOLD signal.&#160;Our laboratory has developed a set of procedures that are capable of overcoming most of these possible issues. For electrical stimulation, a homemade tungsten bipolar microelectrode is used, inserted stereotactically at the stimulation site in the anesthetized subject. In preparation for imaging, rodents are fixed on a plastic headpiece and transferred to the magnet bore. For sedation and paralysis during scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused, along with a minimal dose of isoflurane; this preparation minimizes the BOLD ceiling effect of volatile anesthetics. In this example experiment, stimulation of the subthalamic nucleus (STN) produces BOLD responses which are observed primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous DBS and fMRI allows the unambiguous modulation of neural circuits dependent on stimulation location and stimulation parameters, and permits observation of neuronal modulations free of regional bias. This technique may be used to explore the downstream effects of modulating neural circuitry at nearly any brain region, with implications for both experimental and clinical DBS.

Representative functional data were acquired according to the above protocol in a single rat with a stimulating electrode implanted to the subthalamic nucleus on the right side. An illustration of essential setup for DBS fMRI image acquisition is provided in Figure 1. Stimulation was applied consistent with the above protocol, with an amplitude of 0.3 mA, frequency of 130 Hz and pulse width of 0.09 msec. Robust activation of ipsilateral motor cortex has been consistently visualized using this protocol wi...

This protocol describes a standard method for simultaneous functional magnetic resonance imaging and deep brain stimulation in the rodent. The combined use of these experimental tools allows for the exploration of global downstream activity in response to electrical stimulation at virtually any brain target.

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for ...

Hi, I'm John Ya.And I'm Dan Alba. Today we'll demonstrate functional MRI will. Simultaneous deep brain stimulation in a rat.We can use this technique to map functional responses throughout the brain to deep brain stimulation at a variety of targets. This procedure involves stereotactic electrode implantation FMRI acquisition, an analysis of functional responses. The first step is electrode implantation.We will implant an electrode unilaterally into the subthalamic nucleus. We will start by anesthetizing the animal completely and monitoring physiological parameters, including oxygenation and body temperature throughout the procedure. Begin preparing the surgical site by removing hair and attach the animal to a stereotactic frame.Use ointment to lubricate the animal's eyes during the procedure. Apply antiseptic to the site and apply drapes to the sterilized field. To complete preparation of the surgical site.Remove the skin and fascia overlying the skull, ensuring that bgma and lambda are uncovered. Use a scalpel to roughen the skull surface to improve cement attachment later in the procedure. And use sterile cotton in electrocautery for hemostasis over the bone surface and cut tissues use.Use a needle attached to the stereotactic arm to touch the exact location of bgma as a reference for craniotomy location and mark the location on the skull with the needle for the subthalamic nucleus. This will be 3.6 millimeters posterior torema and 2.5 millimeters lateral from the midline. Use a small bit drill to make a small hole in the skull cleaning and probing the edges of the hole.Use a small gauge needle to thoroughly perturb the dural surface and clean any additional bleeding or leakage of cerebral spinal fluid. Now we will place an MRI compatible screw in the skull for anchoring. Drill a hole in the skull contralateral and posterior to the future electrode location.Place the screw deep enough to be secure, but without pressing on dura or cortex, we use an MRI compatible homemade two channel tungsten micro electrode for stimulation. Inspect the electrode to ensure it is straight and the leads are not split. Place the electrode on the stereotactic arm in a vertical position and touch the tip to bgma.Move the electrode to the position of the target brain region using the stereotactic frame for measurement and touch the cortical surface. Lower the electrode using the stereotactic frame for measurement. Ensure that there is no bending in the electrode.During this process, place an initial layer of cement first, ensuring a dry skull service. After the first layer is dry, bend the electrode posteriorly, then apply additional cement to increase stability. Allow the cement to dry completely before animal removal.The animal may now be resuscitated or immediately prepared for functional MRI scanning. The second step is preparing the animal for FMRI and FMRI acquisition. This may be performed immediately after surgery or several days later.A headpiece should be used to completely immobilize the animal's head with respect to the coil. The animal should be endotracheally, intubated and ventilated. A variety of anesthetics may be used.We use dme, toine, and combin with low dose isof. Fluorine paralysis should be performed using pantonium acquire cap geometry near the junction of the ventilation tubing with the endotracheal tube. Adjust ventilator settings to stabilize end TAL CO2.In the normal range, generally near 3%temperatures should be monitored using a rectal probe fixed to the base of the tail. A circulating hot water bath should be adjusted to stabilize body temperature within the normal range. Pulse oximetry may also be acquired in the hind paw area, placed toothpaste over the area to be scanned to improve image quality.Place a surface coil directly over the brain regions to be scanned. Secure the coil firmly to the headpiece and holder. Connect the stimulating system to the electrode connector and secure the leads in place.Cover the animal for improved insulation in the chilled environment of the magnet. Now it is time to insert the animal into the center of the magnet. Use a three plain S scout image for precise positioning of the animal within the scanner globally.Shim with reference to the cortical surface to improve homogeneity of the magnetic field. Then use FMAP to shim locally at the brain regions to be used for functional scans. Acquire a single T two weighted slice in a mid sagittal plane.Create a single shot gradient. Echo EPI scan with matrix size of 96 by 96, field of view of 2.56 by 2.56 centimeters. Repetition time of 1000 milliseconds, echo time of 14 milliseconds and slice width of one millimeter with four dummy scans followed by 70 repetitions.Each scan with these parameters should last one second. For a total scan time of 70 seconds align this EPI scan to the anterior commissure of the previous T two sagittal image for geometrical consistency between subjects set up stimulation, frequency, pulse width and stimulation paradigm, and synchronize the stimulations trigger to the RF outputs from the scan sequence. Here we use a frequency of 130 hertz pulse width of 90 microseconds and a stimulation paradigm of 60 seconds of rest, followed by 30 seconds of stimulation, and finally 120 seconds of rest.Then set up the stimulation current type, including the desired current amplitude and bipolar current output run. The EPI scan ensuring that the stimulation triggers appropriately after acquisition check to ensure a robust response using the data analysis tools described in the following section. If this does not occur, check the stimulator connections.After all scans are required, anatomical scans should be run to measure approximate electrode position and ensure electrode position within the intended target. Afterward, the rat may be resuscitated and preserved for further experiments. Finally, after all necessary experiments have been run, the animal may be euthanized in the brain perfuse with formalin.With the electrode tract removed, hide resolution T two weighted scans may be performed to identify the electrode tract and its relationship to nearby structures. In this case, the electrode tract terminates just ventral to the internal capsule in the subthalamic nucleus confirming implantation accuracy. Next, we'll process and analyze the results of our functional scans.For this, we'll use a custom written program which runs within matlab, though other software packages for FMRI analysis may be used in a similar fashion in matlab. Use SPM codes to apply rigid body across all stimulus trials. Then create an average segment of images, conserving the time course of the scans, manually perform skull stripping after application of a cutoff threshold.Now we will generate correlation coefficient maps for the brain regions of interest. Noise reduction may be performed using a minimum cluster size or three by three low pass smoothing. The stimulation paradigm should be input and a short paradigm delay may be set to account for hemodynamic delay.For each voxel, the correlation coefficient of signal intensity change over time may then be calculated with respect to the stimulation paradigm. This may be mapped out over each slice to identify neuro anatomical regions where ball response strongly correlates to the experimental protocol. Regions of interest may be manually defined or use a polygon as an approximation.Percent signal change within this region of interest may then be determined using the pre stimulation signal as a baseline. These values may then be exported for statistical analysis. Here we have performed deep brain stimulation at the subthalamic nucleus and the responses on our correlation coefficient map are in brain regions distant from that nucleus.Here we see positive, bold, and cortical regions anterior to the location of stimulation in the most posterior slice. The artifact from the stimulating electrode is visible when the change in bold signal intensity over time is calculated for a sample cortical region of interest. The result is displayed on screen with the stimulation paradigm displayed here by a yellow bar.This may be used to quantify the bold response and for further analysis, we have just demonstrated deep brain stimulation with simultaneous functional MRI in er rodent model. Thank you for watching and good luck with your experiments.I.

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Research

JoVE Journal

Neuroscience

We have developed a method for simultaneous functional magnetic resonance imaging and electrophysiological recording in the rodent brain, providing a platform for the investigation of the relationship between neural activity and the blood oxygenation level dependent (BOLD) MRI signal.

Simultaneous fMRI and Electrophysiology in the Rodent Brain

Source: Casquero-Veiga, M. et al. In vivo Positron Emission Tomography to Reveal Activity Patterns Induced by Deep Brain Stimulation in Rats. J. Vis. Exp. (2022).This video demonstrates the metabolic effects of deep brain stimulation (DBS) using FDG-PET imaging in a rat model. It outlines the steps involved in FDG administration, DBS application, and PET/CT imaging to map brain regions with increased or suppressed metabolic activity.

Assessing Metabolic Neuromodulation Induced by Acute Deep Brain Stimulation in Rats Using In Vivo FDG-PET

Source: Batra, V., et al. A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration. J. Vis. Exp. (2016).This video demonstrates a rat model of drug addiction in which the animal self-administers intravenous methamphetamine by pressing a lever, leading to compulsive drug-seeking behavior driven by dopamine release in the nucleus accumbens. To counteract this, the rat undergoes deep brain stimulation (DBS) via an implanted bipolar...

Deep Brain Stimulation as a Treatment for Drug Addiction in a Rat Model

Source: Selvakumar, T., et al., Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus. J. Vis. Exp. (2015)This video demonstrates the procedure for implanting electrodes into the rat brain to apply deep brain stimulation (DBS), which modulates neuronal activity and enhances communication with the hippocampus, supporting neuronal survival and neurogenesis.

Effects of Deep Brain Stimulation on Hippocampal Neuronal Activity in a Rat Model

The mechanism underlying the therapeutic effects of Deep Brain Stimulation (DBS) surgery needs investigation. The methods presented in this manuscript describe an experimental approach to examine the cellular events triggered by DBS by analyzing the gene expression profile of candidate genes that can facilitate neurogenesis post DBS surgery.

Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

A method for implanting electrodes into the subthalamic nucleus (STN) of rats is described. Better localization of the STN was achieved by using a microrecording system. Furthermore, a stimulation set-up is presented that is characterized by long-lasting connections between the head of the animal and the stimulator.

Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation

This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

This protocol describes a surgical set-up for a permanent epicranial electrode socket and an implanted chest electrode in rodents. By placing a second electrode into the socket, different types of transcranial electrical brain stimulation can be delivered to the motor system in alert animals through the intact skull.

Transcranial Electrical Brain Stimulation in Alert Rodents

This protocol describes the quantification of volumetric cerebral hemodynamic variations in the mouse brain using functional ultrasound (fUS). Procedures for 3D functional activation map following sensory stimulation as well as resting-state functional connectivity are provided as illustrative examples, in anesthetized and awake mice.

Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging

This protocol describes a method for obtaining stable resting-state functional magnetic resonance imaging (rs-fMRI) data from a rat using low dose isoflurane in combination with low dose dexmedetomidine.

Acquisition of Resting-State Functional Magnetic Resonance Imaging Data in the Rat

We describe a preclinical experimental method to evaluate metabolic neuromodulation induced by acute deep brain stimulation with in vivo FDG-PET. This manuscript includes all experimental steps, from stereotaxic surgery to the application of the stimulation treatment and the acquisition, processing, and analysis of PET images.

In vivo Positron Emission Tomography to Reveal Activity Patterns Induced by Deep Brain Stimulation in Rats

Learn deep brain stimulation with simultaneous fMRI in rodents to map brain responses across multiple targets. This method enables real-time analysis of functional connectivity and neural activity patterns.

Deep Brain Stimulation with Simultaneous fMRI in Rodents

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