Name: operative technique and nuances for the stereoelectroencephalographic (seeg) methodology utilizing a robotic stereotactic guidance system
Uploaded: 2023-06-09T13:30:00
Description: Watch this Scientific Journal Video about Operative Technique and Nuances for the Stereoelectroencephalographic SEEG Methodology Utilizing a Robotic Stereotactic Guidance System at JoVE.com

The authors have no acknowledgements.

All devices used herein are FDA approved and the protocol contained herein constitutes the standard of care at our institution. As such, no IRB approval was needed for the detailing of this protocol.
1. Pre-implantation phase
<ol>
	<li>Create an anatamo-electro-clinical (AEC) hypothesis. 
	NOTE: Creation of the AEC hypothesis relies on the coordination of multiple non-invasive techniques for identifying the potential EZ. A team of experts, including epileptologists, radiologists, and ep...

<ol>
	<li>World Health Organization. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Epilepsy. , (2018).</li><li>Talairach, J., Bancaud, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereotaxic+approach+to+epilepsy.">Stereotaxic approach to epilepsy.</a> Progress in neurological surgery. 5, 297-354 (1973).</li><li>Bancaud, J., Talairach, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+organization+of+the+supplementary+motor+area.+Data+obtained+by+stereo-E.E.G.">Functional organization of the supplementary motor area. Data obtained by stereo-E.E.G.</a> Neurochirurgie. 13, 343-356 (1967).</li><li>Jehi, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Epileptogenic+Zone:+Concept+and+Definition.">The Epileptogenic Zone: Concept and Definition.</a> Epilepsy Currents. 18 (1), 12-16 (2018).</li><li>Nowell, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+method+for+implementation+of+frameless+StereoEEG+in+epilepsy+surgery.">A novel method for implementation of frameless StereoEEG in epilepsy surgery.</a> Operative Neurosurgery. 10 (4), 525-534 (2014).</li><li>Abel, T. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Frameless+robot-assisted+stereoelectroencephalography+in+children:+technical+aspects+and+comparison+with+Talairach+frame+technique.">Frameless robot-assisted stereoelectroencephalography in children: technical aspects and comparison with Talairach frame technique.</a> Journal of Neurosurgery: Pediatrics. 1, 1-10 (2018).</li><li>van der Loo, L. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Methodology,+outcome,+safety+and+in+vivo+accuracy+in+traditional+frame-based+stereoelectroencephalography.">Methodology, outcome, safety and in vivo accuracy in traditional frame-based stereoelectroencephalography.</a> Acta neurochirurgica. 159 (9), 1733-1746 (2017).</li><li>Gonz&#225;lez-Mart&#237;nez, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Technique,+results,+and+complications+related+to+robot-assisted+stereoelectroencephalography.">Technique, results, and complications related to robot-assisted stereoelectroencephalography.</a> Neurosurgery. 78 (2), 169-180 (2015).</li><li>Mullin, J. P., Smithason, S., Gonzalez-Martinez, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereo-electro-encephalo-graphy+(SEEG)+with+robotic+assistance+in+the+presurgical+evaluation+of+medical+refractory+epilepsy:+a+technical+note.">Stereo-electro-encephalo-graphy (SEEG) with robotic assistance in the presurgical evaluation of medical refractory epilepsy: a technical note.</a> Journal of visualized experiments. , 112 (2016).</li><li>Jones, J. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Techniques+for+placement+of+stereotactic+electroencephalographic+depth+electrodes:+Comparison+of+implantation+and+tracking+accuracies+in+a+cadaveric+human+study.">Techniques for placement of stereotactic electroencephalographic depth electrodes: Comparison of implantation and tracking accuracies in a cadaveric human study.</a> Epilepsia. 59 (9), 1667-1675 (2018).</li><li>Mullin, J. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Is+SEEG+safe?+A+systematic+review+and+meta-analysis+of+stereo-electroencephalography-related+complications.">Is SEEG safe? A systematic review and meta-analysis of stereo-electroencephalography-related complications.</a> Epilepsia. 57 (3), 386-401 (2016).</li><li>Serletis, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+stereotactic+approach+for+mapping+epileptic+networks:+a+prospective+study+of+200+patients.">The stereotactic approach for mapping epileptic networks: a prospective study of 200 patients.</a> Journal of Neurosurgery. 121, 1239-1246 (2014).</li><li>Taussig, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereo-electroencephalography+(SEEG)+in+65+children:+an+effective+and+safe+diagnostic+method+for+pre-surgical+diagnosis,+independent+of+age.">Stereo-electroencephalography (SEEG) in 65 children: an effective and safe diagnostic method for pre-surgical diagnosis, independent of age.</a> Epileptic Disorders. 16, 280-295 (2014).</li><li>Munyon, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+3-dimensional+grid:+a+novel+approach+to+stereoelectroencephalography.">The 3-dimensional grid: a novel approach to stereoelectroencephalography.</a> Neurosurgery. 11, 127-133 (2015).</li><li>Ortler, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Frame-based+vs+frameless+placement+of+intrahippocampal+depth+electrodes+in+patients+with+refractory+epilepsy:+a+comparative+in+vivo+(application)+study.">Frame-based vs frameless placement of intrahippocampal depth electrodes in patients with refractory epilepsy: a comparative in vivo (application) study.</a> Neurosurgery. 68, 881-887 (2011).</li></ol>

Meticulously defining of the AEC hypothesis coupled with particularly detailed attention to the design of the implantation strategy is ultimately what will determine the success of the SEEG methodology for each individual patient. As such, careful pre-surgical planning of the procedure is critical and makes for a relatively simple, low-risk surgery. Generally it is best to orient the trajectories orthogonally to the sagittal midline, thereby facilitating an easier anatomo-electrophysiological correlation in the future an...

Medically refractory epilepsy (MRE) is estimated to afflict fifteen million people world-wide1. Many of these patients, therefore, may well be treated with surgery. Epilepsy surgery relies on the precise localization of the theorized epileptogenic zone (EZ) in order to guide surgical resections. Jean Tailarach and Jean Bancaud developed the stereoelectroencephalography (SEEG) methodology in the 1950s as a method for more accurately localizing the EZ based on the in situ electrophysiology of the epileptic brain in both cortical and deep structures2,3. However, only recently has the SEEG methodology started to gain favor across North America4.
Various techniques and technologies are used throughout the world as part of the SEEG methodology, based on the clinical experience of different professionals and epilepsy centers5,6,7. Recently, however, there has been an evolution of the surgical techniques used to implant SEEG electrodes, beyond the classical use manual headframe based strategies. Specifically, the use of robotic stereotactic guidance systems has been shown to be an accurate alternative for SEEG implantation8. Robotic implantation can be safely and effectively used by those with surgical expertise who are looking for a faster, more automated, approach to electrode implantation.
Herein is discussed the specific steps undertaken when employing the use of a robotic stereotactic guidance system for the implantation of SEEG electrodes. Though the SEEG methodology has previously been described, herein particular attention is given to the surgical technique employed with the use of the robot9.

<table>
	<tbody>
		<tr>
			<td>2 mm drill bit</td>
			<td>DIXI</td>
			<td>KIP-ACS-510</td>
			<td>For opening the cranium</td>
		</tr>
		<tr>
			<td>Coagulation Electrode Dura</td>
			<td>DIXI</td>
			<td>KIP-ACS-600</td>
			<td>for opening and coagulating the dura</td>
		</tr>
		<tr>
			<td>Cordless driver</td>
			<td>Stryker</td>
			<td>4405-000-000</td>
			<td>to drive the drill bit</td>
		</tr>
		<tr>
			<td>Leksell Coordinate Frame G</td>
			<td>Elekta</td>
			<td>14611</td>
			<td>For head fixation</td>
		</tr>
		<tr>
			<td>Microdeep Depth Electrode</td>
			<td>DIXI</td>
			<td>D08-**AM</td>
			<td>SEEG electrodes that are implanted, complete with: guide bolt and stylet, as described in manuscript.</td>
		</tr>
		<tr>
			<td>ROSA</td>
			<td>Medtech</td>
			<td>n/a</td>
			<td>stereotactic guidance system with robotic arm, complete with: robotic arm, calibration tool, registration laser, head frame attachment, and software, as described in the manuscript.</td>
		</tr>
		<tr>
			<td>Stylet</td>
			<td>DIXI</td>
			<td>ACS-770S-10</td>
			<td>for creating a path through the parenchyma for the electrode</td>
		</tr>
	</tbody>
</table>

operative technique and nuances for the stereoelectroencephalographic (seeg) methodology utilizing a robotic stereotactic guidance system

The SEEG methodology has gained favor in North America over the last decade as a means of localizing the epileptogenic zone (EZ) prior to epilepsy surgery. Recently, the application of a robotic stereotactic guidance system for implantation of SEEG electrodes has become more popular in many epilepsy centers. The technique for the use of the robot requires extreme precision in the pre-surgical planning phase and then the technique is streamlined during the operative portion of the methodology, as the robot and surgeon work in concert to implant the electrodes. Herein is detailed precise operative methodology of using the robot to guide implantation of SEEG electrodes. A major limitation of the procedure, namely its heavy reliance on the ability to register the patient to a preoperative volumetric magnetic resonance image (MRI), is also discussed. Overall, this procedure has been shown to have a low morbidity rate and an extremely low mortality rate. The use of a robotic stereotactic guidance system for the implantation of SEEG electrodes is an efficient, fast, safe, and accurate alternative to conventional manual implantation strategies.

The absolute indicator of success following use of the SEEG methodology is seizure freedom for the patient, which ultimately follows successful electrode implantations, successful electrophysiological recordings, as well as successful resection of the EZ. Such a case is shown in Figure 1. Panels A and B of Figure 1 show two tests (single positron emission computed tomography (SPECT) and magnetoelectroencephalography (MEG), respec...

Watch this Scientific Journal Video about Operative Technique and Nuances for the Stereoelectroencephalographic SEEG Methodology Utilizing a Robotic Stereotactic Guidance System at JoVE.com

Operative Technique and Nuances for the Stereoelectroencephalographic SEEG Methodology Utilizing a Robotic Stereotactic Guidance System

The SEEG methodology is simplified and made faster with a stereotactic robot. Careful attention must be paid to the registration of the preoperative volumetric MRI to the patient prior to use of the robot in the OR. The robot streamlines the procedure, leading to decreased operative times and accurate implantations.

Operative Technique and Nuances for the Stereoelectroencephalographic (SEEG) Methodology Utilizing a Robotic Stereotactic Guidance System

The SEEG methodology has gained favor in North America over the last decade as a means of localizing the epileptogenic zone (EZ) prior to epilepsy ...

SEEG, also known as stereoelectroencephalography, is a minimally invasive method of exploration of the human brain that takes into account the three-dimensional aspect of the epileptiform activity by analyzing the anatomoelectroclinical correlations. The main advantage of this method is to map epileptiform discharges in the brain in a minimally invasive fashion. Before beginning the SEEG procedure, help the patient into the supine position.With the patient under general anesthesia, fix the patient's head in a three-point fixation holder and position the robot at the head of the patient such that the distance between the base of the robotic arm and the midpoint of the cranium is 70 centimeters. Lock the robot into position and secure the three-point head holder to the robot. Using the semi-automatic laser-based facial recognition system, register the pre-operative volumetric MRI with the patient, following all of the prompts given by the robot.Use the set-distance calibration tool to calibrate the laser and use the laser to manually select the preset anatomical facial landmarks. After the robot automatically scans the facial surface, correlate additional independent surface landmarks with the registered MRI to confirm the accuracy of the registration. For bolt implantation, drape the patient in standard sterile fashion and drape the robotic working arm with sterile plastic.Attach a drilling platform with a 2.5-millimeter working cannula to the robotic arm and select the desired trajectory for each bolt to be implanted on the touchscreen of the robot. Step on the robot pedal to initiate the movement of the robotic arm to the first trajectory. When the correct position is reached, the arm will be automatically locked by the robot.Insert a two-millimeter drill through the working cannula and use it to create a pinhole through the entire thickness of the skull. Open the dura with an insulated dural perforator using monopolar cautery at a low setting. Screw the guide bolt firmly into each pinhole and use a sterile ruler to measure the distance from the drilling platform to the guide bolt.Subtract this measured distance from the value of the distance platform-to-target used in planning the trajectory and record the result for later use as the final length of the implanted electrode. Measure and note the final length of the electrode and confirm that it matches the newly calculated length for the bolt. Then, give the electrode and bolt matching labels to prevent confusion during the electrode implantation.When all of the bolts have been implanted, change surgical gloves and open a new sterile field. Insert a two-millimeter diameter stylet through a guide bolt to the intended depth of the electrode, as calculated after implantation of the matching bolt. Confirm that the electrode to be implanted matches the label of the implanted guide bolt and remove the stylet.Immediately insert the electrode through the bolt and screw the electrode into the bolt for fixation, using fluoroscopic x-ray to confirm the correct placement of each electrode after it has been implanted. When all of the electrodes have been implanted, use a standard head bandaging technique to wrap the patient's head. Here, an appropriate operating room set up with a successful bolt placement and a successful electrode implantation for the SEEG methodology is shown.Single positron emission computed tomography and magnetoelectroencephalography tests help in the creation of the anatomoelectroclinical hypothesis. In these representative images, an electrode was positioned in the frontal opercular and dorsal insular area. Here, a resection of the right operculum and insula in a post-operative T1 MRI is shown.The SEEG method allows the three-dimensional mapping of the epileptiform activity by applying a minimally invasive technique of placing depth electrodes into the human brain.

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Research

JoVE Journal

Behavior

Stereotactic Injection of MicroRNA-expressing Lentiviruses to the Mouse Hippocampus CA1 Region and Assessment of the Behavioral Outcome

MicroRNAs (miRNAs) are small regulatory single-stranded RNA molecules around 22 nucleotides long that may each target numerous mRNA transcripts and dim an entire gene expression pathway by inducing destruction and/or inhibiting translation of these targets. Several miRNAs play key roles in maintaining neuronal structure and function and in higher-level brain functions, and methods are sought for manipulating their levels for exploring these functions. Here, we present a direct in vivo method for examining the cognitive consequences of enforced miRNAs excess in mice by stereotactic injection of miRNA-encoding virus particles. Specifically, the current protocol involves injection into the hippocampal CA1 region, which contributes to mammalian memory consolidation, learning, and stress responses, and offers a convenient injection site. The coordinates are measured according to the mouse bregma and virus perfusion is digitally controlled and kept very slow. After injection, the surgery wound is sealed and the animals recover. Lentiviruses encoding silencers of the corresponding mRNA targets serve to implicate the specific miRNA/target interaction responsible for the observed effect, with na&iuml;ve mice, mice injected with saline and mice injected with "empty" lentivirus vectors as controls. One month post-injection, the animals are examined in the Morris Water Maze (MWM) for assessing their navigation learning and memory abilities. The MWM is a round tank filled with colored water with a small platform submerged 1 cm below the water surface. Steady visual cues around the tank allow for spatial navigation (sound and the earth's magnetic field may also assist the animals in navigating). Video camera monitoring enables measuring the route of swim and the time to find and amount the platform. The mouse is first taught that mounting the hidden platform offers an escape from the enforced swimming; it is then tested for using this escape and finally, the platform is removed and probe tests examine if the mouse remembers its previous location. Repeated tests over several consecutive days highlight improved performance of tested mice at shorter latencies to find and mount the platform, and as more direct routes to reach the platform or its location. Failure to show such improvement represents impaired learning and memory and/or anxiety, which may then be tested specifically (e.g. in the elevated plus maze). This approach enables validation of specific miRNAs and target transcripts in the studied cognitive and/or stress-related processes.

MicroRNAs have significant roles in brain structure and function. Here we describe a method to enforce hippocampal miRNA over-expression using stereotactic injection of an engineered miRNA-expressing lentivirus. This approach can serve as a relatively rapid way to assess the in vivo effects of over-expressed miRNAs in specific brain regions.

MicroRNAs (miRNAs) are small regulatory single-stranded RNA molecules around 22 nucleotides long that may each target numerous mRNA transcripts and dim an ...

Contextual and Cued Fear Conditioning Test Using a Video Analyzing System in Mice

The contextual and cued fear conditioning test is one of the behavioral tests that assesses the ability of mice to learn and remember an association between environmental cues and aversive experiences. In this test, mice are placed into a conditioning chamber and are given parings of a conditioned stimulus (an auditory cue) and an aversive unconditioned stimulus (an electric footshock). After a delay time, the mice are exposed to the same conditioning chamber and a differently shaped chamber with presentation of the auditory cue. Freezing behavior during the test is measured as an index of fear memory. To analyze the behavior automatically, we have developed a video analyzing system using the ImageFZ application software program, which is available as a free download at http://www.mouse-phenotype.org/. Here, to show the details of our protocol, we demonstrate our procedure for the contextual and cued fear conditioning test in C57BL/6J mice using the ImageFZ system. In addition, we validated our protocol and the video analyzing system performance by comparing freezing time measured by the ImageFZ system or a photobeam-based computer measurement system with that scored by a human observer. As shown in our representative results, the data obtained by ImageFZ were similar to those analyzed by a human observer, indicating that the behavioral analysis using the ImageFZ system is highly reliable. The present movie article provides detailed information regarding the test procedures and will promote understanding of the experimental situation.

This article presents a protocol for a contextual and cued fear conditioning test using a video analyzing system to assess fear learning and memory in mice.

The contextual and cued fear conditioning test is one of the behavioral tests that assesses the ability of mice to learn and remember an association ...

Assessment of Murine Exercise Endurance Without the Use of a Shock Grid: An Alternative to Forced Exercise

Using laboratory mouse models, the molecular pathways responsible for the metabolic benefits of endurance exercise are beginning to be defined. The most common method for assessing exercise endurance in mice utilizes forced running on a motorized treadmill equipped with a shock grid. Animals who quit running are pushed by the moving treadmill belt onto a grid that delivers an electric foot shock; to escape the negative stimulus, the mice return to running on the belt. However, avoidance behavior and psychological stress due to use of a shock apparatus can interfere with quantitation of running endurance, as well as confound measurements of postexercise serum hormone and cytokine levels. Here, we demonstrate and validate a refined method to measure running endurance in na&#239;ve C57BL/6 laboratory mice on a motorized treadmill without utilizing a shock grid. When mice are preacclimated to the treadmill, they run voluntarily with gait speeds specific to each mouse. Use of the shock grid is replaced by gentle encouragement by a human operator using a tongue depressor, coupled with sensitivity to the voluntary willingness to run on the part of the mouse. Clear endpoints for quantifying running time-to-exhaustion for each mouse are defined and reflected in behavioral signs of exhaustion such as splayed posture and labored breathing. This method is a humane refinement which also decreases the confounding effects of stress on experimental parameters.

A method to assess exercise endurance in laboratory mice without the use of a shock grid is demonstrated. This method is a humane refinement that can decrease the confounding effects of stress on experimental parameters.

Using laboratory mouse models, the molecular pathways responsible for the metabolic benefits of endurance exercise are beginning to be defined. The most ...

Practical Methodology of Cognitive Tasks Within a Navigational Assessment

This paper describes an approach for measuring navigation accuracy relative to cognitive skills. The methodology behind the assessment will thus be clearly outlined in a step-by-step manner. Navigational skills are important when trying to find symbols within a speech-generating device (SGD) that has a dynamic screen and taxonomical organization. The following skills have been found to impact children&#8217;s ability to find symbols when navigating within the levels of an SGD: sustained attention, categorization, cognitive flexibility, and fluid reasoning1,2. According to past studies, working memory was not correlated with navigation1,2.
The materials needed for this method include a computerized tablet, an augmentative and alternative communication application, a booklet of symbols, and the Leiter International Performance Scale-Revised (Leiter-R)3. This method has been used in two previous studies. Robillard, Mayer-Crittenden, Roy-Charland, Minor-Corriveau and B&#233;langer1 assessed typically developing children, while Rondeau, Robillard and Roy-Charland2 assessed children and adolescents with a diagnosis of Autism Spectrum Disorder. The direct observation of this method will facilitate the replication of this study for researchers. It will also help clinicians that work with children who have complex communication needs to determine the children&#8217;s ability to navigate an SGD with taxonomical categorization.

Children who have complex communication needs can benefit from the use of a speech-generating device (SGD). Cognitive skills were identified as having an impact on the ability to navigate between levels of SGDs. This protocol describes the steps needed for Speech-language Pathologists to assess cognitive skills and navigational abilities.

This paper describes an approach for measuring navigation accuracy relative to cognitive skills. The methodology behind the assessment will thus be ...

Applying Stereotactic Injection Technique to Study Genetic Effects on Animal Behaviors

Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or knockdown gene expression in a relatively focused region without significant damage to the brain tissue. After recovery, the injected mouse can be tested on various behavioral tasks such as the Open Field Test (OFT) and the Forced Swim Test (FST). The OFT is designed to assess locomotion and the anxious phenotype in mice by measuring the amount of time that a mouse spends in the center of a novel open field. A more anxious mouse will spend significantly less time in the center of the novel field compared to controls. The FST assesses the anti-depressive phenotype by quantifying the amount of time that mice spend immobile when placed into a bucket of water. A mouse with an anti-depressive phenotype will spend significantly less time immobile compared to control animals. The goal of this protocol is to use the stereotactic injection of a lentivirus in conjunction with behavioral tests to assess how genetic factors modulate animal behaviors.

Stereotactic injection of lentiviruses expressing cDNAs or shRNAs can modulate gene expression in specific brain areas of mice. Here, we present a protocol to combine stereotactic injections with behavioral tasks, such as the Open Field Test (OFT) and the Forced Swim Test (FST).

Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or ...

Investigating Motor Skill Learning Processes with a Robotic Manipulandum

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be time-intensive and ambiguous to quantify beyond simple success rates. Here, we describe the training procedure for reach-and-pull tasks with ETH Pattus, a robotic platform for automated forelimb reaching training that records pulling and hand rotation movements in rats. Kinematic quantification of the performed pulling attempts reveals the presence of distinct temporal profiles of movement parameters such as pulling velocity, spatial variability of the pulling trajectory, deviation from midline, as well as pulling success. We show how minor adjustments in the training paradigm result in alterations in these parameters, revealing their relation to task difficulty, general motor function or skilled task execution. Combined with electrophysiological, pharmacological and optogenetic techniques, this paradigm can be used to explore the mechanisms underlying motor learning and memory formation, as well as loss and recovery of function (e.g. after stroke).

A paradigm is presented for training and analysis of an automated skilled reaching task in rats. Analysis of pulling attempts reveals distinct subprocesses of motor learning.

Skilled reaching tasks are commonly used in studies of motor skill learning and motor function under healthy and pathological conditions, but can be ...

Utilizing the Modified T-Maze to Assess Functional Memory Outcomes After Cardiac Arrest

Background: Evaluating mild to moderate cognitive impairment in a global cerebral ischemia (i.e. cardiac arrest) model can be difficult due to poor locomotion after surgery. For example, rats who undergo surgical procedures and are subjected to the Morris water maze may not be able to swim, thus voiding the experiment.
New Method: We established a modified behavioral spontaneous alternation T-maze test. The major advantage of the modified T-maze protocol is its relatively simple design that is powerful enough to assess functional learning/memory after ischemia. Additionally, the data analysis is simple and straightforward. We used the T-maze to determine the rats&#39; learning/memory deficits both in the presence or absence of mild to moderate (6 min) asphyxial cardiac arrest (ACA). Rats have a natural tendency for exploration and will explore the alternate arms in the T-maze, whereas hippocampal-lesioned rats tend to adopt a side-preference resulting in decreased spontaneous alternation ratios, revealing the hippocampal-related functional learning/memory in the presence or absence of ACA.
Results: ACA groups have higher side-preference ratios and lower alternations as compared to control.
Comparison with Existing Method(s): The Morris water and Barnes maze are more prominent for assessing learning/memory function. However, the Morris water maze is more stressful than other mazes. The Barnes maze is widely used to measure reference (long-term) memory, while ACA-induced neurocognitive deficits are more closely related to working (short-term) memory.
Conclusions: We have developed a simple, yet effective strategy to delineate working (short-term) memory via the T-maze in our global cerebral ischemia model (ACA).

This protocol describes the use of a modified T-maze to evaluate functional learning/memory in asphyxia cardiac arrest-induced cerebral ischemia.

Background: Evaluating mild to moderate cognitive impairment in a global cerebral ischemia (i.e. cardiac arrest) model can be difficult due to poor ...

Methodology for Establishing a Community-Wide Life Laboratory for Capturing Unobtrusive and Continuous Remote Activity and Health Data

An end-to-end suite of technologies has been established for the unobtrusive and continuous monitoring of health and activity changes occurring in the daily life of older adults over extended periods of time. The technology is aggregated into a system that incorporates the principles of being minimally obtrusive, while generating secure, privacy protected, continuous objective data in real-world (home-based) settings for months to years. The system includes passive infrared presence sensors placed throughout the home, door contact sensors installed on exterior doors, connected physiological monitoring devices (such as scales), medication boxes, and wearable actigraphs. Driving sensors are also installed in participants' cars and computer (PC, tablet or smartphone) use is tracked. Data is annotated via frequent online self-report options that provide vital information with regard to the data that is difficult to infer via sensors such as internal states (e.g., pain, mood, loneliness), as well as data referent to activity pattern interpretation (e.g., visitors, rearranged furniture). Algorithms have been developed using the data obtained to identify functional domains key to health or disease activity monitoring, including mobility (e.g., room transitions, steps, gait speed), physiologic function (e.g., weight, body mass index, pulse), sleep behaviors (e.g., sleep time, trips to the bathroom at night), medication adherence (e.g., missed doses), social engagement (e.g., time spent out of home, time couples spend together), and cognitive function (e.g., time on computer, mouse movements, characteristics of online form completion, driving ability). Change detection of these functions provides a sensitive marker for the application in health surveillance of acute illnesses (e.g., viral epidemic) to the early detection of prodromal dementia syndromes. The system is particularly suitable for monitoring the efficacy of clinical interventions in natural history studies of geriatric syndromes and in clinical trials.

Unobtrusive sensors and pervasive computing technology incorporated into the daily home life of older adults enables meaningful health and activity changes to be recorded continuously for months to years, providing ecologically valid, high frequency, multi-domain data for research or clinical use.

An end-to-end suite of technologies has been established for the unobtrusive and continuous monitoring of health and activity changes occurring in the ...

Tickling, a Technique for Inducing Positive Affect When Handling Rats

Handling small animals such as rats can lead to several adverse effects. These include the fear of humans, resistance to handling, increased injury risk for both the animals and the hands of their handlers, decreased animal welfare, and less valid research data. To minimize negative effects on experimental results and human-animal relationships, research animals are often habituated to being handled. However, the methods of habituation are highly variable and often of limited effectiveness. More potently, it is possible for humans to mimic aspects of the animals&#39; playful rough-and-tumble behavior during handling. When applied to laboratory rats in a systematic manner, this playful handling, referred to as tickling, consistently gives rise to positive behavioral responses. This article provides a detailed description of a standardized rat tickling technique. This method can contribute to future investigations into positive affective states in animals, make it easier to handle rats for common husbandry activities such as cage changing or medical/research procedures such as injection, and be implemented as a source of social enrichment. It is concluded that this method can be used to efficiently and practicably reduce rats&#39; fearfulness of humans and improve their welfare, as well as reliably model positive affective states.

This article demonstrates the standardized application of playful handling, a tickling technique designed to mimic rat rough-and-tumble play. This technique is effective at reducing fearful reactions to humans and generating positive affect when rats are handled for common husbandry activities and medical and research procedures such as injection.

Handling small animals such as rats can lead to several adverse effects. These include the fear of humans, resistance to handling, increased injury risk ...

A Middle Cerebral Artery Occlusion Technique for Inducing Post-stroke Depression in Rats

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of all ischemic stroke patients suffer from PSD, a disorder considered to be an ischemic stroke-related precursor for increased death and degradation in health. The pathophysiology of PSD is still obscure. To study the mechanism of development and occurrence of PSD further, and to find out a therapy, we attempted to develop a new protocol that requires occluding the middle cerebral artery (MCA) via the internal carotid artery (ICA) in rats. This protocol describes a model of PSD induced in rats through the middle cerebral artery occlusion (MCAO). Also used in the experiment are the Porsolt forced swim test and the sucrose preference test to confirm and evaluate the depressive mood of the rats under investigation. Rather than inserting the catheter through the external carotid artery (ECA), as stipulated for the original procedure, this MCAO technique has the monofilament passing directly through the ICA. This MCAO technique was developed a few years ago and leads to a reduction in mortality and variability. It is generally accepted that the criteria used are preferred in the selection of biological models. The data obtained with this protocol show that this model of MCAO could be a way of inducing PSD in rats and could potentially lead to the understanding of the pathophysiology and the future development of new drugs and other neuroprotective agents.

Here we present a protocol to induce post-stroke depression in rats by occluding the middle cerebral artery via the internal carotid artery. We use the Porsolt forced swim test and the sucrose preference test to confirm and evaluate induced depressive moods.

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of ...