Name: application of 3d printing in the construction of burr hole ring for deep brain stimulation implants
Uploaded: 2019-09-07T13:00:00
Description: Watch this Scientific Journal Video about Application of 3D Printing in the Construction of Burr Hole Ring for Deep Brain Stimulation Implants at JoVE.com

This work is supported by grants from Natural Science Fund of Guangdong Province (No. 2017A030313597) and Southern Medical University (No. LX2016N006, No. KJ20161102).

1. Drawing a two dimensional (2D)-image of a burr hole ring
<ol>
	<li>Open the 2D computer aided design (CAD) software and then create a graphical document.</li>
	<li>Click Draw | Line and draw a reference point with a solid line on the drawing. Click Modify | Offset, and type the specific offset distance in the command line.</li>
	<li>Click on the object and press by the left mouse button to create a solid line. Click Modify | Trim, select the area to be trimmed and c...

<ol>
	<li>Pucci, J. U., Christophe, B. R., Sisti, J. A., Connolly, E. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Three-dimensional+printing:+technologies,+applications,+and+limitations+in+neurosurgery.">Three-dimensional printing: technologies, applications, and limitations in neurosurgery.</a> Biotechnology Advances. 35 (5), 521-529 (2017).</li><li>Mashiko, T., 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=Development+of+three-dimensional+hollow+elastic+model+for+cerebral+aneurysm+clipping+simulation+enabling+rapid+and+low+cost+prototyping.">Development of three-dimensional hollow elastic model for cerebral aneurysm clipping simulation enabling rapid and low cost prototyping.</a> World Neurosurgery. 83 (3), 351-361 (2015).</li><li>Chae, M. 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=Emerging+Applications+of+Bedside+3D+Printing+in+Plastic+Surgery.">Emerging Applications of Bedside 3D Printing in Plastic Surgery.</a> Frontiers in Surgery. 2, 25 (2015).</li><li>Doyle, B. 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=Improved+assessment+and+treatment+of+abdominal+aortic+aneurysms:+the+use+of+3D+reconstructions+as+a+surgical+guidance+tool+in+endovascular+repair.">Improved assessment and treatment of abdominal aortic aneurysms: the use of 3D reconstructions as a surgical guidance tool in endovascular repair.</a> Irish Journal of Medical Science. 178 (3), 321-328 (2009).</li><li>Kimura, T., 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=Simulation+of+and+training+for+cerebral+aneurysm+clipping+with+3-dimensional+models.">Simulation of and training for cerebral aneurysm clipping with 3-dimensional models.</a> Neurosurgery. 65 (4), 719-725 (2009).</li><li>Park, E. K., 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=Cranioplasty+Enhanced+by+Three-Dimensional+Printing:+Custom-Made+Three-Dimensional-Printed+Titanium+Implants+for+Skull+Defects.">Cranioplasty Enhanced by Three-Dimensional Printing: Custom-Made Three-Dimensional-Printed Titanium Implants for Skull Defects.</a> Journal of Craniofacial Surgery. 27 (4), 943-949 (2016).</li><li>Ray, C. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Burr-hole+ring-cap+and+electrode+anchoring+device.+Technical+note.">Burr-hole ring-cap and electrode anchoring device. Technical note.</a> Journal of Neurosurgery. 55 (6), 1004-1006 (1981).</li><li>Yamamoto, T., Katayama, Y., Kobayashi, K., Oshima, H., Fukaya, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dual-floor+burr+hole+adjusted+to+burr-hole+ring+and+cap+for+implantation+of+stimulation+electrodes.+Technical+note.">Dual-floor burr hole adjusted to burr-hole ring and cap for implantation of stimulation electrodes. Technical note.</a> Journal of Neurosurgery. 99 (4), 783-784 (2003).</li><li>Wharen, R. E., Putzke, J. D., Uitti, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+brain+stimulation+lead+fixation:+a+comparative+study+of+the+Navigus+and+Medtronic+burr+hole+fixation+device.">Deep brain stimulation lead fixation: a comparative study of the Navigus and Medtronic burr hole fixation device.</a> Clinical Neurology and Neurosurgery. 107 (5), 393-395 (2005).</li><li>Patel, N. V., Barrese, J., Ditota, R. J., Hargreaves, E. L., Danish, S. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+brain+stimulation+lead+fixation+after+Stimloc+failure.">Deep brain stimulation lead fixation after Stimloc failure.</a> Journal of Clinical Neuroscience. 19 (12), 1715-1718 (2012).</li><li>Chen, 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=3-D+printing+for+constructing+the+burr+hole+ring+of+lead+fixation+device+in+deep+brain+stimulation.">3-D printing for constructing the burr hole ring of lead fixation device in deep brain stimulation.</a> Journal of Clinical Neuroscience. 58, 229-233 (2018).</li><li>Hoang, D., Perrault, D., Stevanovic, M., Ghiassi, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+applications+of+three-dimensional+printing:+a+review+of+the+current+literature+&amp;+how+to+get+started.">Surgical applications of three-dimensional printing: a review of the current literature &amp; how to get started.</a> Annals of Translational Medicine. 4 (23), (2016).</li><li>Bustamante, S., Bose, S., Bishop, P., Klatte, R., Norris, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+application+of+rapid+prototyping+for+simulation+of+bronchoscopic+anatomy.">Novel application of rapid prototyping for simulation of bronchoscopic anatomy.</a> Journal of Cardiothoracic and Vascular Anesthesia. 28 (4), 1122-1125 (2014).</li><li>Lan, Q., 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=Development+of+Three-Dimensional+Printed+Craniocerebral+Models+for+Simulated+Neurosurgery.">Development of Three-Dimensional Printed Craniocerebral Models for Simulated Neurosurgery.</a> World Neurosurgery. 91, 434-442 (2016).</li><li>Li, W. Z., Zhang, M. C., Li, S. P., Zhang, L. T., Huang, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Application+of+computer-aided+three-dimensional+skull+model+with+rapid+prototyping+technique+in+repair+of+zygomatico-orbito-maxillary+complex+fracture.">Application of computer-aided three-dimensional skull model with rapid prototyping technique in repair of zygomatico-orbito-maxillary complex fracture.</a> The International Journal of Medical Robotics. 5 (2), 158-163 (2009).</li><li>Wang, L., Cao, T., Li, X., Huang, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Three-dimensional+printing+titanium+ribs+for+complex+reconstruction+after+extensive+posterolateral+chest+wall+resection+in+lung+cancer.">Three-dimensional printing titanium ribs for complex reconstruction after extensive posterolateral chest wall resection in lung cancer.</a> The Journal of Thoracic and Cardiovascular Surgery. 152 (1), e5-e7 (2016).</li><li>Xu, N. F., 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=Reconstruction+of+the+Upper+Cervical+Spine+Using+a+Personalized+3D-Printed+Vertebral+Body+in+an+Adolescent+With+Ewing+Sarcoma.">Reconstruction of the Upper Cervical Spine Using a Personalized 3D-Printed Vertebral Body in an Adolescent With Ewing Sarcoma.</a> Spine. 41 (1), E50-E54 (2016).</li><li>Brozova, H., Barnaure, I., Alterman, R. L., Tagliati, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=STN-DBS+frequency+effects+on+freezing+of+gait+in+advanced+Parkinson+disease.">STN-DBS frequency effects on freezing of gait in advanced Parkinson disease.</a> Neurology. 72 (8), 770 (2009).</li><li>Moreau, 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=STN-DBS+frequency+effects+on+freezing+of+gait+in+advanced+Parkinson+disease.">STN-DBS frequency effects on freezing of gait in advanced Parkinson disease.</a> Neurology. 71 (2), 80-84 (2008).</li><li>Oyama, G., 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=Unilateral+GPi-DBS+as+a+treatment+for+levodopa-induced+respiratory+dyskinesia+in+Parkinson+disease.">Unilateral GPi-DBS as a treatment for levodopa-induced respiratory dyskinesia in Parkinson disease.</a> Neurologist. 17 (5), 282-285 (2011).</li></ol>

These results showed that the software used were practicable to build 3D models of burr hole rings (Figure 1 and Figure 2), and 3D printing can be used to build solid models with designated materials (Figure 4). In terms of the size of the solid model, there was an absolute error from 0 to 0.59 mm determined through the measurement made by Vernier calipers (Figure 6). To some extent, the error is unavoi...

3D printing has been applied in the medical field since the 1980s, especially in surgery for preoperative simulation, anatomical learning and surgical training1. For example, in cerebrovascular operations, preoperative simulation can be conducted by using 3D printed vascular models2. With the development of 3D printing, the texture, temperature, structure and weight of cerebral blood vessels can be simulated to the greatest extent of clinical scenarios. Trainees can perform surgical operations such as cutting and clamping on such models. This training is very important for the surgeons3,4,5. Currently, titanium patches formed by 3D printing have also gradually been applied6, since the skull prostheses developed by 3D printing after imaging and reconstruction are highly conformal. However, the development and application of 3D printing in neurosurgery is still limited.
The burr hole ring, as a part of the lead fixation device, has been widely used in deep brain stimulation (DBS)7,8,9,10. However, current burr hole rings are made by medical device manufacturers according to the unified specifications and dimensions. This standard burr hole ring is not always suitable for all conditions, such as skull malformation and scalp atrophy. It may increase the uncertainties of operation and reduce the acurracy. The emergence of 3D printing makes it possible to develop individualized burr hole rings for patients in clinical scenarios5. At the same time, the burr hole ring, which is not easy to obtain, is not conducive to extensive preoperative demonstration and surgical training1.
To address the problems mentioned above, we proposed to construct a burr hole ring with 3D printing. A previous study in our lab described an innovative burr hole ring for DBS11. In this study, this innovative burr hole ring will be regarded as an excellent example to exhibit the detailed production process. Therefore, the purpose of this study is to provide a modeling process and a detailed technical process of building a solid burr hole ring using 3D printing.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Adobe Photoshop Version 14.0</td>
			<td>Adobe System&#65292;US</td>
			<td>_</td>
			<td>Only available with a paid subscription.</td>
		</tr>
		<tr>
			<td>Allcct 3D printer</td>
			<td>Allcct technology co., LTD, WuHan, China</td>
			<td>201807A794124CN</td>
			<td></td>
		</tr>
		<tr>
			<td>Allcct_YinKe_V1.1</td>
			<td>Allcct technology co., LTD, WuHan, China</td>
			<td></td>
			<td>The software is provided by the 3D printer manufacturer and there is no Catalog number associated with it</td>
		</tr>
		<tr>
			<td>AutoCAD 2004</td>
			<td>Autodesk co., LTD&#65292;US</td>
			<td>666-12345678</td>
			<td>Software for 2D models</td>
		</tr>
		<tr>
			<td>Carbon Fibre</td>
			<td>Allcct technology co., LTD, WuHan, China</td>
			<td>PLA175&#216;5181&#216;3&#216;B</td>
			<td>The material is provided by the 3D printer manufacturer</td>
		</tr>
		<tr>
			<td>Netfabb Studio Basic 4.9</td>
			<td>Autodesk co., LTD&#65292;US</td>
			<td>-</td>
			<td>The software is provided by a 3D printer manufacturer and is open to access</td>
		</tr>
		<tr>
			<td>Pro/E 2001</td>
			<td>Parametric Technology Corporation, PTC, US</td>
			<td>_</td>
			<td>Software for 3D models; Only available with a paid subscription.</td>
		</tr>
		<tr>
			<td>Vernier caliper&#160;</td>
			<td>&#160;Beijing Blue Light Machinery Electricity Instrument Co,. LTD, China</td>
			<td>GB/T&#8194;1214.1-1996&#8194;</td>
			<td></td>
		</tr>
	</tbody>
</table>

application of 3d printing in the construction of burr hole ring for deep brain stimulation implants

3D printing has been widely applied in the medical field since the 1980s, especially in surgery, such as preoperative simulation, anatomical learning and surgical training. This raises the possibility of using 3D printing to construct a neurosurgical implant. Our previous works took the construction of the burr hole ring as an example, described the process of using softwares like computer aided design (CAD), Pro/Engineer (Pro/E) and 3D printer to construct physical products. That is, a total of three steps are required, the drawing of 2D-image, the construction of 3D-image of burr hole ring, and using a 3D printer to print the physical model of burr hole ring. This protocol shows that the burr hole ring made of carbon fiber can be rapidly and accurately molded by 3D printing. It indicated that both CAD and Pro/E softwares can be used to construct the burr hole ring via integrating with the clinical imaging data and further applied 3D printing to make the individual consumables.

Three views of 2D images were built through commercial CAD software (see the Table of Materials). In these images, practical size and technical requirements have also been added (Figure 1). Further, three-dimensional data were constructed in (Figure 2) and saved in STL format (Figure 3). As presented in Figure 4, solid parts were built on the platform of...

Watch this Scientific Journal Video about Application of 3D Printing in the Construction of Burr Hole Ring for Deep Brain Stimulation Implants at JoVE.com

Application of 3D Printing in the Construction of Burr Hole Ring for Deep Brain Stimulation Implants

Here, we present a protocol to demonstrate 3D printing in the construction of deep brain stimulation implants.

3D printing has been widely applied in the medical field since the 1980s, especially in surgery, such as preoperative simulation, anatomical learning and ...

3D printing make possible to develop individualized burr hole rings for patients. Our protocol provide the detailed procedures for using 3D model program to construct these implants. 3D printing objects have a high product efficiency, a low cost and are customizable.With the help of 3D printing, patients can obtain implants that are highly specific to their individual needs. To draw a 2D image of a burr hole ring, open a new graphical document in the 2D CAD software program. Click Draw and Line and draw a reference point with a solid line on the drawing.Then click Modify and Offset and type the specific offset distance in the command line. To select the area to be trimmed, click Modify and Trim and click the extra line. To draw the top view, click Draw and Line to construct the reference point and click Daw, Circle and Center Diameter to input the quantitative value of the specific radius of the circle or diameter in the command window.Then click the center of the reference point to form a circle. Next, draw the left view of the inner burr hole ring using the same approach as that for the front view. Click Dimension and Diameter and click on the circumference to mark the diameter of the circle.Click on Dimension and Linear to mark the length and thickness of all of the associated structures. Then click Dimension and Radius to mark the angle of the chamber. Using the same protocol, construct 2D drawings of the outer burr hole ring and mark the actual size and the labeling.Then click Save to save the 2D image of the burr hole ring. To draw a 3D image of the burr hole ring, open the 3D drawing software program and select the front plane as the sketch plane. Click Default under Sket view and select the dotted line tool to draw the top section of the part in the two-dimensional sketch.Click Conform and Done and click the datum plane icon. In the menu manager, select Create, Solid, Add Sheet, Rotate and Done. Then click Bilateral in the Properties menu and click Done.To construct the cross-section of the hook of the outer burr hole ring, click Front, Forward, Default, Datum Plane and Dotted Line. Click Confirm and Done and enter 50 in angle and indicated direction 45 and click Done in the protrusion. Then click the coloring button.Next select Redefine in the part feature and click the line structure of the hook. Select Section, Define and Sketch. Click the dotted line icon.Create two square embossments on the hook section, click OK, Done and Coloring. Click the datum access icon and click Insert a Datum and Cross. Click the center axis of the line structure.Click angle in the datum plane and click the front plane in the line structure view. Then click Input Value in the Offset menu and enter minus 45 in angle and indicated direction 45. Click Features, Copy and Mirror.Click the hook as the object and click Done Select and Done. Click the datum plane to complete the copy and copy the remaining two hooks in the same manner. Then click Create Concentric Circle to construct a circle with a radius of 7.23 millimeters and click the segmentation of primitives at selected points icon to remove the unnecessary lines of the circle.To create a complete outer wall section, click the solid line button and click OK and Done. Enter four as the enter depth and click Coloring. Click Mirror and Done.Click the object and Done. Then click the datum plane to complete the copy. To confirm, click Copy, Mirror and Done and select two outer walls in different directions.Then click Done and click the datum plane to complete the copy. To enhance the graphic details, click View, Model Settings, Color and Appearance, Add and adjust the RGB color slider to brown. Then click Close, Settings and OK.Click the Eliminating Hidden Lines button and click the Create Concentric Circle.Continue to create an outer edge on the outer wall and click the Segmentation of Primitives at Selected Points button to remove excess lines. Click the Solid Line button to connect the newly added outer edge into a complete section and click OK.Enter 0.8 as the enter depth and click OK in the protrusion window. In the menu manager, click Copy, Mirror, Done, click the object and click Done.Click Generate Benchmark and Offset and click the input value in Offset. Then enter 0.4 as the isometric of the specified direction and click Done. Click Copy, Mirror and Done and click the outer wall.To complete the mirror operation of the outer wall and the square embossing, click Done Select and Done and click the datum of the image to complete the copy. Select File and Copy and save the file in stl format. Enter the part number and click OK.Then in the output STL dialogue box, adjust the cord height to 006 and the angle control to 0.00001, click Apply and OK.To print the rings, open the project files in the model detecting software.Confirm that the outer ring is complete and click Part, Export Part as STL and Save. Following model detection, open the slicing software and click File and Load Model File and open one stl file. Click the left mouse button to select the moving track of the part and adjust the position of parts.Set the print speed to 30 millimeters per second, the printing temperature to 210 degrees Celsius and the bed temperature to 80 degrees Celsius. Then click Tool Path to SD to save the file in G-code format and to generate the printed path. When the temperature rises to the preset value, click Print and select the target file and Confirm to start printing.After the bottom supporting grid has been constructed, the printing nozzle will begin to construct the outer ring vertically, layer by layer. After the outer ring is formed, the printer nozzle will print the inner ring on the right side. After both rings have cooled, remove the models from the platform.Here, the absolute error and error range were calculated for five groups of parts that were produced as demonstrated. The results indicate that in the outer ring, the maximum absolute error and minimum absolute error were found in the outside diameter of the waist and in the thickness of the top respectively. In the inner ring, the maximum absolute error and the minimum absolute error were found in the inside diameter and in the thickness of the top respectively.The total error range was 0.00, 0.59.3D and MR data has a potential to be used to build the actual imaging of the burr hole rings if the thick can be extract from images. Our protocol provides a rapid and accurate method for constructing deep brain stimulation implants through the integration of clinical imaging data and 3D printing.

application-3d-printing-construction-burr-hole-ring-for-deep-brain

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 ...

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal&#8217;s behavioral profile can be investigated in one single test.
The apparatus consists of a box, representing the &#8216;protected&#8217; area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the &#8216;unprotected&#8217; area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals&#8217; adaptive capacities.
Due to testing order effects in a behavioral test battery, na&#239;ve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress.

This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities.

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.

Vagus nerve stimulation (VNS) has emerged as a tool to induce targeted synaptic plasticity in the forebrain to modify a range of behaviors. This protocol describes how to implement VNS to facilitate the consolidation of fear extinction memory.

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been ...

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

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. 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. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

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.

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people.  There is a need ...

Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function

Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose- and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects.

Non-invasive electrical brain stimulation can modulate cortical function and behavior, both for research and clinical purposes. This protocol describes different brain stimulation approaches for modulation of the human motor system.

Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, ...

Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression.
Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil.

Here we present a protocol outlining the methodology for treatment of Major Depressive Disorder using the deep Transcranial Magnetic Stimulation (dTMS) system.

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses ...

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson&#39;s lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way.

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, which is unlike the protocols used for human subjects. We report a successful application of rTMS to the unilateral hemisphere of rat brain. The rTMS was delivered with a low-frequency (1 Hz), high-frequency (20 Hz), or sham stimulation protocol to one side of the brain by using a small 25-mm figure-8 coil. We placed the center of the coil 1 cm lateral to the vertex on the biauricular line and angulated the coil 45&#176; to the ground to minimize a potential direct effect of rTMS on the contralateral cortex. We also used an in-house water cooling system to enable repetitive magnetic stimulation for more than 20 min, even at a 20-Hz stimulation frequency. Increases in the transcriptions of immediate early genes (Arc, Junb, and Egr2) were greater after rTMS than after sham stimulation. After 5 consecutive days of 20-min 1-Hz rTMS, bdnf mRNA expression was significantly higher in stimulated cortex than in contralateral side. The model presented herein will elucidate the molecular mechanisms of rTMS by allowing analysis of the inter-hemispheric difference in its effect.

We applied repetitive transcranial magnetic stimulation (rTMS) to the unilateral hemisphere of rat brain, by placing a 25-mm figure-8 coil 1 cm lateral to the vertex on the biauricular line and angulating the coil by 45&#176;. An in-house water cooling system was used for rTMS for more than 20 min.

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, ...

How to Use the H1 Deep Transcranial Magnetic Stimulation Coil for Conditions Other than Depression

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The coils are made of soft copper windings in multiple planes that lie adjacent to the skull. They are located within a special helmet so that their magnetic fields combine and improve depth penetration. The H1 dTMS coil is designed to stimulate bilateral prefrontal cortices with greater effective stimulation over the left than the right. By positioning the left side of the coil close to the left dorsolateral prefrontal cortex (DLPFC), the H1 coil was used in a multisite study, leading to FDA approval for treatment-resistant depression. In this same position, the H1 coil was also explored as a possible treatment for negative symptoms of schizophrenia, bipolar depression, and migraine. When moved to different positions over the subject's skull, the H1 coil was also explored as a possible treatment for other conditions. Such manipulation of the H1 coil was demonstrated for PTSD and alcohol dependence by positioning it over the medial prefrontal cortex (mPFC), for anxiety by positioning it over the right prefrontal cortex (rPFC), for auditory hallucinations and tinnitus by positioning it over the temporoparietal junction (TPJ), and for Parkinson's and fatigue from multiple sclerosis (MS) by positioning it over the motor cortex (MC) and PFC. Corresponding electrical field diagrams measured with an oscilloscope through a saline-filled head are included.

The H1 deep transcranial magnetic stimulation coil is FDA-cleared for the treatment of depression. We demonstrate how to utilize the H1 for other conditions, such as auditory hallucinations and PTSD, by moving the helmet to different locations over the subject's skull.

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The ...

Simultaneous Transcranial Alternating Current Stimulation and Functional Magnetic Resonance Imaging

Transcranial alternating current stimulation (tACS) is a promising tool for noninvasive investigation of brain oscillations. TACS employs frequency-specific stimulation of the human brain through current applied to the scalp with surface electrodes. Most current knowledge of the technique is based on behavioral studies; thus, combining the method with brain imaging holds potential to better understand the mechanisms of tACS. Because of electrical and susceptibility artifacts, combining tACS with brain imaging can be challenging, however, one brain imaging technique that is well suited to be applied simultaneously with tACS is functional magnetic resonance imaging (fMRI). In our lab, we have successfully combined tACS with simultaneous fMRI measurements to show that tACS effects are state, current, and frequency dependent, and that modulation of brain activity is not limited to the area directly below the electrodes. This article describes a safe and reliable setup for applying tACS simultaneously with visual task fMRI studies, which can lend to understanding oscillatory brain function as well as the effects of tACS on the brain.

Transcranial alternating current stimulation (tACS) is a promising tool for noninvasive investigation of brain oscillations, though its effects are not completely understood. This article describes a safe and reliable setup for applying tACS simultaneously with functional magnetic resonance imaging, which can increase understanding oscillatory brain function and effects of tACS.