The authors thank all the clinical teams contributing daily to the care of neurovascular patients at UCSD.

1. Simulator setup
<ol>
	<li>Prior to all procedures, assemble the simulator as shown in Figure 1 and turn on. Refer to Table 1 for the full list of simulator equipment needed to complete each simulation.</li>
	<li>Select the patient scenario using the software interface on the attached laptop (Figure 1C).</li>
	<li>Select the appropriate arterial sheath or guide catheter&#160;from the drop-down menu. This does not need to be physically inserted as part of the simulation, but will act as the femoral access site and allow subsequent entry of wires and catheters into the system (Figure 1D). Specific sheath/guide sizes for each scenario are discussed below.</li>
	<li>Select the appropriate catheter(s), guidewire, and/or microsystem based on the specific scenario as discussed below (Figure 1D).</li>
	<li>Turn on A (PA) and B plane (lateral) fluoroscopy on the software interface. Activate the fluoroscopy with the foot pedals (Figure 1H) and adjust both the patient and image intensifier positions with the joysticks (Figure 1I) until the correct PA and lateral views are obtained.</li>
</ol>
2. First patient scenario: Four-vessel angiography
NOTE:&#160;This scenario depicts a 52-year-old male with an unruptured left carotid terminus aneurysm found incidentally on a non-contrast computed tomography (CT) scan of the head.
<ol>
	<li>Select a 5-French femoral sheath, a 0.035 in guidewire, and a 4-French diagnostic catheter from the drop-down menu as tools to be used in this simulation.</li>
	<li>Insert the guidewire into the simulator machine (Figure 1D) until it registers on the simulation screen, signaling that access has been gained. Advance the guidewire until it is visualized in the descending thoracic aorta and continues into the aortic arch.</li>
	<li>When the guidewire is safely in the aortic arch, hold the guidewire in place and insert a diagnostic catheter over the guidewire through the simulated femoral sheath to the aortic arch.</li>
	<li>Remove the guidewire and utilize the fluoroscopy puff technique by gently pressing the contrast syringe (Figure 1E) to simulate contrast injection and briefly opacify the vessels as the catheter is advanced into the desired artery.</li>
	<li>Next, create a roadmap guide&#160;injecting contrast with the contrast syringe (Figure 1E) while the fluoroscopy foot pedal is depressed (Figure 1H). Next, reinsert the wire to selectively catheterize the desired vessel, advancing the catheter over the wire. Remove the wire for subsequent angiography runs.&#160;The right and left internal and external carotid arteries and the right and left vertebral arteries are all catheterized using this&#160;technique.</li>
	<li>Using the diagnostic catheter and the simulator contrast syringe (Figure 1E), perform angiograms of each of the above circulations by depressing the fluoroscopy pedal (Figure 1H) while injecting contrast with the syringe. Obtain high-magnification views of the aneurysm, if necessary. Review angiograms for adequacy prior to removing the catheter.</li>
	<li>Once the necessary images are obtained, remove the diagnostic catheter/guidewire from the simulation sheath. Simulated closure of the femoral arteriotomy site is not performed.</li>
</ol>
3. Second patient scenario: Carotid terminus aneurysm coiling
NOTE:&#160;This scenario depicts a 52-year-old male with a known ruptured left carotid terminus aneurysm, severe headache, nonfocal exam, and a Glasgow Coma Scale score of 15.
<ol>
	<li>Select a&#160;6-French guide catheter, 0.035 in guidewire, and a 4-French diagnostic catheter, from the drop-down menu.</li>
	<li>Insert a diagnostic catheter over a guidewire into the aortic arch as in steps 2.2&#8211;2.3.</li>
	<li>Insert a guide catheter over the diagnostic catheter through the femoral access site (Figure 1D) to the aortic arch.</li>
	<li>Remove the guidewire and create a roadmap guide of the left common carotid artery by roadmap flourscopy foot pedal&#160;injecting contrast with the contrast syringe (Figure 1E) while the fluoroscopy foot pedal (Figure 1H) is depressed.</li>
	<li>Reinsert the guidewire and selectively catheterize the left common carotid artery and internal carotid artery using fluoroscopy and the roadmap overlay visualized on the image projection monitor (Figure 1B) by leading with the guidewire and advancing the diagnostic catheter and guide catheter once safe access is gained.</li>
	<li>When the guide catheter is within the internal carotid artery, remove the diagnostic catheter and wire and perform angiographic runs of the left internal carotid cerebral circulation by depressing the fluoroscopy pedal (Figure 1H) while injecting contrast with the syringe (Figure 1E).</li>
	<li>Measure the aneurysm using the calculation option on the software interface (Figure 1C). Keeping in mind that the coil diameter for the first coil should be 1 mm wider than the mean&#160;aneurysm diameter, select an appropriate coil.</li>
	<li>Select a microcatheter and microwire from the drop-down menu.</li>
	<li>Insert the&#160;microcatheter and microwire through the femoral access site (Figure 1D), and under roadmap guidance obtained as in step 3.6, selectively catheterize the aneurysm with the microsystem.</li>
	<li>Remove the microwire, insert the previously selected coil through the femoral access site (Figure 1D), and advance it slowly into the aneurysm.</li>
	<li>Once the coil is fully inserted, perform a diagnostic cerebral angiogram by depressing the fluoroscopy pedal (Figure 1H) while injecting contrast with the syringe and assess the patency of the parent artery and aneurysm filling. The goal is to maintain patency of the parent artery and either completely embolize the aneurysm or provide sufficient coverage of the dome or presumed rupture point to appropriately reduce rupture risk.</li>
	<li>Detach the coil on the software interface (Figure 1C) and remove the coil wire. If necessary, repeat steps 3.11 and 3.12 with additional coils until ~30% aneurysm occlusion is obtained.</li>
	<li>Remove the microcatheter and guide catheter from the simulation sheath site (Figure 1D). Simulated closure of the femoral arteriotomy site is not performed.</li>
</ol>
4. Third patient scenario: Left middle cerebral artery thrombectomy
NOTE: This scenario depicts a 64-year-old female with a National Institutes of Health Stroke Scale (NIHSS) score of 12 for aphasia and right-sided weakness who was last known to be normal 4 h earlier. Head CT revealed a hyperdense left middle cerebral artery (MCA) sign and an Alberta Stroke Program Early CT score (ASPECTS) of 10, but no hemorrhage. A CT angiogram demonstrated a left M1 segment complete occlusion.
<ol>
	<li>Select a&#160;6-French guide catheter,&#160; 0.035 in guidewire, and a 4-French diagnostic catheter,&#160;from the drop-down menu.</li>
	<li>Insert the guide catheter into the left internal carotid artery and perform angiographic runs of the left internal carotid cerebral circulation as described in steps 3.2&#8211;3.6.</li>
	<li>Select a microcatheter/microwire and a stent retriever device from the drop down menu.&#160;</li>
	<li>Insert the microcatheter and microwire into the simulated femoral access site (Figure 1D) and into the left internal carotid artery.</li>
	<li>Under roadmap guidance obtained as in step 3.5, advance the microwire and microcatheter into the left MCA and carefully past the area of occlusion. Potential complications during this maneuver include vascular perforations and/or embolizing a clot downstream.</li>
	<li>Remove the microwire and insert a stent retriever device into the simulated femoral access site (Figure 1D) and advance into the MCA distal to the occlusion. Then, remove the microcatheter, leaving the stent retriever in place at the level of the occlusion.</li>
	<li>Turn on simulated aspiration on the software interface (Figure 1C), and retract the stent retriever device into the guide&#160;catheter by pulling back on the microwire.</li>
	<li>Remove both the stent retriever from the simulated femoral access site (Figure 1D).</li>
	<li>Perform an angiogram through the guide catheter by depressing the fluoroscopy pedal (Figure 1H) while injecting contrast with the syringe to ensure removal of the occlusion.</li>
	<li>Remove the guide catheter from the simulation sheath site (Figure 1D). Simulated closure of the femoral arteriotomy site is not performed.</li>
</ol>

<ol>
	<li>See, K. W., Chui, K. H., Chan, W. H., Wong, K. C., Chan, Y. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evidence+for+Endovascular+Simulation+Training:+A+Systematic+Review.">Evidence for Endovascular Simulation Training: A Systematic Review.</a> European Journal of Vascular and Endovascular Surgery. 51 (3), 441-451 (2016).</li><li>Pannell, J. S., 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=Simulator-Based+Angiography+and+Endovascular+Neurosurgery+Curriculum:+A+Longitudinal+Evaluation+of+Performance+Following+Simulator-Based+Angiography+Training.">Simulator-Based Angiography and Endovascular Neurosurgery Curriculum: A Longitudinal Evaluation of Performance Following Simulator-Based Angiography Training.</a> Cureus. 8 (8), 756 (2016).</li><li>Liebig, 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=Metric-Based+Virtual+Reality+Simulation:+A+Paradigm+Shift+in+Training+for+Mechanical+Thrombectomy+in+Acute+Stroke.">Metric-Based Virtual Reality Simulation: A Paradigm Shift in Training for Mechanical Thrombectomy in Acute Stroke.</a> Stroke. 49 (7), 239-242 (2018).</li><li>Spiotta, A. 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=Diagnostic+angiography+skill+acquisition+with+a+secondary+curve+catheter:+phase+2+of+a+curriculum-based+endovascular+simulation+program.">Diagnostic angiography skill acquisition with a secondary curve catheter: phase 2 of a curriculum-based endovascular simulation program.</a> Journal of Neurointerventional Surgery. 7 (10), 777-780 (2015).</li><li>Spiotta, A. M., Rasmussen, P. A., Masaryk, T. J., Benzel, E. C., Schlenk, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simulated+diagnostic+cerebral+angiography+in+neurosurgical+training:+a+pilot+program.">Simulated diagnostic cerebral angiography in neurosurgical training: a pilot program.</a> Journal of Neurointerventional Surgery. 5 (4), 376-381 (2013).</li><li>Fargen, K. 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=Experience+with+a+simulator-based+angiography+course+for+neurosurgical+residents:+beyond+a+pilot+program.">Experience with a simulator-based angiography course for neurosurgical residents: beyond a pilot program.</a> Neurosurgery. 73, 46-50 (2013).</li><li>Fargen, K. 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=Simulator+based+angiography+education+in+neurosurgery:+results+of+a+pilot+educational+program.">Simulator based angiography education in neurosurgery: results of a pilot educational program.</a> Journal of Neurointerventional Surgery. 4 (6), 438-441 (2012).</li><li>Cates, C., L&#246;nn, L., Gallagher, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prospective,+randomised+and+blinded+comparison+of+proficiency-based+progression+full-physics+virtual+reality+simulator+training+versus+invasive+vascular+experience+for+learning+carotid+artery+angiography+by+very+experienced+operators.">Prospective, randomised and blinded comparison of proficiency-based progression full-physics virtual reality simulator training versus invasive vascular experience for learning carotid artery angiography by very experienced operators.</a> BMJ Simulation and Technology Enhanced Learning. 2, 1-5 (2016).</li><li>Guo, J., Jin, X., Guo, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Study+of+the+Operational+Safety+of+a+Vascular+Interventional+Surgical+Robotic+System.">Study of the Operational Safety of a Vascular Interventional Surgical Robotic System.</a> Micromachines. 9 (3), 119 (2018).</li><li>Tedesco, M. 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=Simulation-based+endovascular+skills+assessment:+the+future+of+credentialing.">Simulation-based endovascular skills assessment: the future of credentialing.</a> Journal of Vascular Surgery. 47 (5), 1008 (2008).</li></ol>

AAK has previously received competitive grants from Covidien Ltd. and Penumbra Inc. and holds consulting arrangements for physician training with Stryker Neurovascular, Covidien Ltd., and Penumbra Inc. JSP has served as a medical consultant to Stryker Neurovascular and Dart NeuroScience LLC. AAK and JSP have no direct financial interests related to this work. The remaining authors have no disclosures concerning the materials or methods used in this study or the findings specified in this paper.

Endovascular surgery is an expanding field that offers a minimally invasive treatment approach to a variety of pathologies. The significant risks associated with vascular injuries nonetheless provides unique educational challenges. With advances in simulation-based training, the education of trainees now allows practice in a risk-free environment that mimics real-life cases. Accordingly, endovascular simulation-based training has been shown to consistently improve performance metrics such as procedure time, fluoroscopy t...

Simulation-based training is an established educational tool for medical trainees and is particularly beneficial in high-risk fields such as endovascular neurosurgery. Multiple virtual reality training devices utilizing catheter-based systems exist, such as the ANGIO Mentor simulator (Simbionix Ltd., Airport City, Israel) and VIST-C and VIST G5 simulators (Mentice AB, Gothenburg, Sweden), with a significant body of data demonstrating the utility of training on procedural aptitude1. In spite of the usefulness of the simulators, step-by-step procedural instructions for their use are lacking.
Presented is a detailed protocol for use of the ANGIO Mentor simulator, a system that supports competency improvements in common endovascular neurosurgery procedures including diagnostic cerebral angiograms,&#160;mechanical thrombectomies, and aneurysm coil embolizations2. Prior work shows that after trainees of all levels performed five simulated angiograms, five thrombectomies, and ten aneurysm coil embolizations on the ANGIO Mentor simulator, they displayed significant improvements in procedural time, fluoroscopy and contrast doses, and adverse technical events2.
The following step-by-step instructions are divided into case scenarios and can easily be integrated into an academic training curriculum for medical students, residents, or fellows2. It should nonetheless be noted that a basic understanding of cerebral arterial anatomy, angiography, and stroke and aneurysm treatments is needed to optimize the educational potential of the simulation device.
All procedures described below (i.e., diagnostic cerebral angiogram, coiling of carotid terminus aneurysm, mechanical thrombectomy) can be performed by a single operator using the ANGIO Mentor simulator (Simbionix Ltd.) (Figure 1). This training device allows neurosurgical trainees of all skill levels to gain exposure to endovascular techniques in a preclinical setting, with the three patient scenarios utilized based on a previously published curriculum for simulator-based angiography training2. To reproduce endovascular techniques with high fidelity, the simulator utilizes actual catheters and wires introduced through a port similar to the diaphragm of a femoral artery sheath. The wires and catheters engage internal rollers that record both rotational and translational motions, which are displayed on the monitors. Device selections and patient vital signs are also visible to the simulator operator.

<table>
	<tbody>
		<tr>
			<td>ANGIO Mentor simulator</td>
			<td>Simbionix Ltd., Airport City, Israel</td>
			<td>N/a</td>
			<td>The setup for the ANGIO Mentor simulator includes the simulator housing as pictured in Figure 1: (A), an external monitor for image projection (x-ray, angiography; B), a laptop for interfacing with the Simbionix Software (C), the simulated femoral artery sheath (with an outer guide-catheter, inner diagnostic microcatheter and guidewire shown; D), a contrast syringe (E), an insufflator for balloon inflation (F), a stent delivery device (G; not used in these patient scenarios), foot pedals for fluoroscopy, roadmap guidance, and angiographic runs (H), and the operator control panel on the simulator housing where the operator is able to control patient and image intensifier positioning (I).</td>
		</tr>
	</tbody>
</table>

simulator training for endovascular neurosurgery

Simulation-based training has become common practice across medical specialties, especially for learning complex skills performed in high-risk environments. In the field of endovascular neurosurgery, the demand for consequence- and risk-free learning environments led to the development of simulation devices valuable for medical trainees. The goal of this protocol is to provide instructive guidelines for the use of an endovascular neurosurgery simulator in an academic setting. The simulator provides trainees with the opportunity to receive realistic feedback on their knowledge of anatomy, as well as haptic feedback indicative of their success in handling the catheter-based systems without negative consequences. The utility of this specific protocol in relation to other neuroendovascular training modalities is also discussed.

The ANGIO Mentor simulator was previously shown to improve the skills of surgical trainees with varying neuroendovascular experience when performing simulated diagnostic angiograms, thrombectomies, and ruptured aneurysm coil embolizations in an academic setting2. In this study, performance metrics for the aforementioned procedures were established over the course of 30 days in one medical student, one neurosurgery resident, two diagnostic neuroradiology fellows, and one endovascular neurosurgery f...

Watch this Scientific Journal Video about Simulator Training for Endovascular Neurosurgery at JoVE.com

Simulator Training for Endovascular Neurosurgery

Simulation of complex, high-risk procedures is critical to the education of medical trainees. A protocol for simulator-based endovascular neurosurgery training in a controlled academic environment is described. The protocol includes stepwise guidelines for trainees of varying levels, with a discussion of the advantages and limitations of this model.

Simulation-based training has become common practice across medical specialties, especially for learning complex skills performed in high-risk ...

simulator-training-for-endovascular-neurosurgery

Research

JoVE Journal

Neuroscience

3.5K Views.  University of California. Simulation of complex, high-risk procedures is critical to the education of medical trainees. A protocol for simulator-based endovascular neurosurgery training in a controlled academic environment is described. The protocol includes stepwise guidelines for trainees of varying levels, with a discussion of the advantages and limitations of this model.

Video: Simulator Training for Endovascular Neurosurgery

Focal Cerebral Ischemia Model by Endovascular Suture Occlusion of the Middle Cerebral Artery in the Rat

Stroke is the leading cause of disability and the third leading cause of death in adults worldwide1. In human stroke, there exists a highly variable clinical state; in the development of animal models of focal ischemia, however, achieving reproducibility of experimentally induced infarct volume is essential. The rat is a widely used animal model for stroke due to its relatively low animal husbandry costs and to the similarity of its cranial circulation to that of humans2,3. In humans, the middle cerebral artery (MCA) is most commonly affected in stroke syndromes and multiple methods of MCA occlusion (MCAO) have been described to mimic this clinical syndrome in animal models. Because recanalization commonly occurs following an acute stroke in the human, reperfusion after a period of occlusion has been included in many of these models. In this video, we demonstrate the transient endovascular suture MCAO model in the spontaneously hypertensive rat (SHR). A filament with a silicon tip coating is placed intraluminally at the MCA origin for 60 minutes, followed by reperfusion. Note that the optimal occlusion period may vary in other rat strains, such as Wistar or Sprague-Dawley. Several behavioral indicators of stroke in the rat are shown. Focal ischemia is confirmed using T2-weighted magnetic resonance images and by staining brain sections with 2,3,5-triphenyltetrazolium chloride (TTC) 24 hours after MCAO.

Surgical induction of ischemic brain damage in the rat is a widely used model for stroke research. Here we demonstrate the induction of focal cerebral ischemia by occlusion of the middle cerebral artery. Visualization of the resulting infarct by histological staining and magnetic resonance imaging is also shown.

Stroke is the leading cause of disability and the third leading cause of death in adults worldwide1. In human stroke, there exists a highly variable ...

MPI CyberMotion Simulator: Implementation of a Novel Motion Simulator to Investigate Multisensory Path Integration in Three Dimensions

Path integration is a process in which self-motion is integrated over time to obtain an estimate of one's current position relative to a starting point 1. Humans can do path integration based exclusively on visual 2-3, auditory 4, or inertial cues 5. However, with multiple cues present, inertial cues - particularly kinaesthetic - seem to dominate 6-7. In the absence of vision, humans tend to overestimate short distances (&lt;5 m) and turning angles (&lt;30&deg;), but underestimate longer ones 5. Movement through physical space therefore does not seem to be accurately represented by the brain.
Extensive work has been done on evaluating path integration in the horizontal plane, but little is known about vertical movement (see 3 for virtual movement from vision alone). One reason for this is that traditional motion simulators have a small range of motion restricted mainly to the horizontal plane. Here we take advantage of a motion simulator 8-9 with a large range of motion to assess whether path integration is similar between horizontal and vertical planes. The relative contributions of inertial and visual cues for path navigation were also assessed.
16 observers sat upright in a seat mounted to the flange of a modified KUKA anthropomorphic robot arm. Sensory information was manipulated by providing visual (optic flow, limited lifetime star field), vestibular-kinaesthetic (passive self motion with eyes closed), or visual and vestibular-kinaesthetic motion cues. Movement trajectories in the horizontal, sagittal and frontal planes consisted of two segment lengths (1st: 0.4 m, 2nd: 1 m; &plusmn;0.24 m/s2 peak acceleration). The angle of the two segments was either 45&deg; or 90&deg;. Observers pointed back to their origin by moving an arrow that was superimposed on an avatar presented on the screen.
Observers were more likely to underestimate angle size for movement in the horizontal plane compared to the vertical planes. In the frontal plane observers were more likely to overestimate angle size while there was no such bias in the sagittal plane. Finally, observers responded slower when answering based on vestibular-kinaesthetic information alone. Human path integration based on vestibular-kinaesthetic information alone thus takes longer than when visual information is present. That pointing is consistent with underestimating and overestimating the angle one has moved through in the horizontal and vertical planes respectively, suggests that the neural representation of self-motion through space is non-symmetrical which may relate to the fact that humans experience movement mostly within the horizontal plane.

An efficient way to gain insight into how humans navigate themselves in three dimensions is described. The method takes advantage of a motion simulator capable of moving observers in ways unattainable by traditional simulators. Results confirm that movement in the horizontal plane is underestimated, while vertical movement is overestimated.

Path integration is a process in which self-motion is integrated over time to obtain an estimate of one's current position relative to a starting point 1. ...

Extinction Training During the Reconsolidation Window Prevents Recovery of Fear

Fear is maladaptive when it persists long after circumstances have become safe. It is therefore crucial to develop an approach that persistently prevents the return of fear. Pavlovian fear-conditioning paradigms are commonly employed to create a controlled, novel fear association in the laboratory. After pairing an innocuous stimulus (conditioned stimulus, CS) with an aversive outcome (unconditioned stimulus, US) we can elicit a fear response (conditioned response, or CR) by presenting just the stimulus alone1,2 . Once fear is acquired, it can be diminished using extinction training, whereby the conditioned stimulus is repeatedly presented without the aversive outcome until fear is no longer expressed3. This inhibitory learning creates a new, safe representation for the CS, which competes for expression with the original fear memory4. Although extinction is effective at inhibiting fear, it is not permanent. Fear can spontaneously recover with the passage of time. Exposure to stress or returning to the context of initial learning can also cause fear to resurface3,4.
Our protocol addresses the transient nature of extinction by targeting the reconsolidation window to modify emotional memory in a more permanent manner. Ample evidence suggests that reactivating a consolidated memory returns it to a labile state, during which the memory is again susceptible to interference5-9. This window of opportunity appears to open shortly after reactivation and close approximately 6hrs later5,11,16, although this may vary depending on the strength and age of the memory15. By allowing new information to incorporate into the original memory trace, this memory may be updated as it reconsolidates10,11. Studies involving non-human animals have successfully blocked the expression of fear memory by introducing pharmacological manipulations within the reconsolidation window, however, most agents used are either toxic to humans or show equivocal effects when used in human studies12-14. Our protocol addresses these challenges by offering an effective, yet non-invasive, behavioral manipulation that is safe for humans.
By prompting fear memory retrieval prior to extinction, we essentially trigger the reconsolidation process, allowing new safety information (i.e., extinction) to be incorporated while the fear memory is still susceptible to interference. A recent study employing this behavioral manipulation in rats has successfully blocked fear memory using these temporal parameters11. Additional studies in humans have demonstrated that introducing new information after the retrieval of previously consolidated motor16, episodic17, or declarative18 memories leads to interference with the original memory trace14. We outline below a novel protocol used to block fear recovery in humans.

Conditioned fear can be diminished through an inhibitory process called extinction, but can resurface under conditions such as the passage of time or exposure to stress. Our protocol presents a novel way of preventing fear recovery by introducing extinction during the reconsolidation window (the re-storage phase of a reactivated memory).

Fear is maladaptive when it persists long after circumstances have become safe. It is therefore crucial to develop an approach that persistently prevents ...

Exposure of the Pig CNS for Histological Analysis: A Manual for Decapitation, Skull Opening, and Brain Removal

Pigs have become increasingly popular in large-animal translational neuroscience research as an economically and ethically feasible substitute to non-human primates. The large brain size of the pig allows the use of conventional clinical brain imagers and the direct use and testing of neurosurgical procedures and equipment from the human clinic. Further macroscopic and histological analysis, however, requires postmortem exposure of the pig central nervous system (CNS) and subsequent brain removal. This is not an easy task, as the pig CNS is encapsulated by a thick, bony skull and spinal column. The goal of this paper and instructional video is to describe how to expose and remove the postmortem pig brain and the pituitary gland in an intact state, suitable for subsequent macroscopic and histological analysis.

The goal of this paper and instructional video is to describe how to expose and remove the postmortem pig brain and pituitary gland in an intact state, suitable for subsequent macroscopic and histological analysis.

Pigs have become increasingly popular in large-animal translational neuroscience research as an economically and ethically feasible substitute to ...

Comprehensive Endovascular and Open Surgical Management of Cerebral Arteriovenous Malformations

Arteriovenious malformations (AVMs) are associated with significant morbidity and mortality, and have a rupture risk of ~3% per year. Treatment of AVMs must be tailored specifically to the lesion, with surgical resection being the gold standard for small, accessible lesions. Pre-operative embolization of AVMs can reduce nidal blood flow and remove high-risk AVM features such as intranidal or venous aneurysms, thereby simplifying a challenging neurosurgical procedure. Herein, we describe our approach for the staged endovascular embolization and open resection of AVMs, and highlight the advantages of having a comprehensively trained neurovascular surgeon leading a multi-disciplinary clinical team. This includes planning the craniotomy and resection to immediately follow the final embolization stage, thereby using a single session of anesthesia for aggressive embolization, and rapid resection. Finally, we provide a representative case of a 22-year-old female with an unruptured right frontal AVM diagnosed during a seizure workup, who was successfully treated via staged embolizations followed by open surgical resection.

Surgery is the gold standard for accessible arteriovenious malformations (AVMs), and pre-operative embolization can simplify this procedure. We describe our approach for staged endovascular embolization and open resection of AVMs, and provide a representative clinical example highlighting the advantages of a comprehensively trained neurovascular surgeon leading a multi-disciplinary clinical team.

Arteriovenious malformations (AVMs) are associated with significant morbidity and mortality, and have a rupture risk of ~3% per year. Treatment of AVMs ...

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain.

The ability to induce and/or control neural plasticity may be critical in future treatments for neurologic disorders and the recovery from brain injury. In this paper, we present a protocol on the use of neurofeedback training with functional magnetic resonance imaging to modulate human brain function.

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control ...

Fiber Connections of the Supplementary Motor Area Revisited: Methodology of Fiber Dissection, DTI, and Three Dimensional Documentation

The purpose of this study is to show the methodology for the examination of the white matter connections of the supplementary motor area (SMA) complex (pre-SMA and SMA proper) using a combination of fiber dissection techniques on cadaveric specimens and magnetic resonance (MR) tractography. The protocol will also describe the procedure for a white matter dissection of a human brain, diffusion tensor tractography imaging, and three-dimensional documentation. The fiber dissections on human brains and the 3D documentation were performed at the University of Minnesota, Microsurgery and Neuroanatomy Laboratory, Department of Neurosurgery. Five postmortem human brain specimens and two whole heads were prepared in accordance with Klingler's method. Brain hemispheres were dissected step by step from lateral to medial and medial to lateral under an operating microscope, and 3D images were captured at every stage. All dissection results were supported by diffusion tensor imaging. Investigations on the connections in line with Meynert's fiber tract classification, including association fibers (short, superior longitudinal fasciculus I and frontal aslant tracts), projection fibers (corticospinal, claustrocortical, cingulum, and frontostriatal tracts), and commissural fibers (callosal fibers) were also conducted.

The purpose of this study is to show each step of the fiber dissection technique on human cadaveric brains, the 3D documentation of these dissections, and the diffusion tensor imaging of the anatomically dissected fiber pathways.

The purpose of this study is to show the methodology for the examination of the white matter connections of the supplementary motor area (SMA) complex ...

Optimized Management of Endovascular Treatment for Acute Ischemic Stroke

This manuscript describes a streamlined protocol for the management of patients with acute ischemic stroke, which aims at the minimization of time from hospital admission to reperfusion. Rapid restoration of cerebral blood flow is essential for the outcomes of patients with acute ischemic stroke. Endovascular treatment (EVT) has become the standard of care to accomplish this in patients with acute stroke due to large vessel occlusion (LVO). To achieve reperfusion of ischemic brain regions as fast as possible, all in-hospital time delays have to be carefully avoided. Therefore, management of patients with acute ischemic stroke was optimized with an interdisciplinary standard operating procedure (SOP). Stroke neurologists, diagnostic as well as interventional neuroradiologists, and anesthesiologists streamlined all necessary processes from patient admission and diagnosis to EVT of eligible patients. Target times for every step were established. Actually achieved times were prospectively recorded along with clinical data and imaging scores for all endovascularly treated stroke patients. These data were regularly analyzed and discussed in interdisciplinary team meetings. Potential issues were evaluated and all staff involved was trained to adhere to the SOP. This streamlined patient management approach and enhanced interdisciplinary collaboration reduced time from patient admission to reperfusion significantly and was accompanied by a beneficial effect on clinical outcomes.

The outcome of patients with acute ischemic stroke depends on swift restoration of cerebral blood flow. This protocol aims at optimizing the management of such patients by minimizing peri-procedural timings and rendering the time from hospital admission to reperfusion as short as possible.

This manuscript describes a streamlined protocol for the management of patients with acute ischemic stroke, which aims at the minimization of time from ...

Real-Time fMRI Brain Mapping in Animals

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a real-time fMRI platform to guide experimenters to monitor fMRI responses instantaneously during acquisition, which can be used to modify the physiology of animals to achieve desired hemodynamic responses in animal brains. The real-time fMRI set-up is based on a 14.1T preclinical MRI system, enabling the real-time mapping of dynamic fMRI responses in the primary forepaw somatosensory cortex (FP-S1) of anesthetized rats. Instead of a retrospective analysis to investigate confounding sources leading to the variability of fMRI signals, the real-time fMRI platform provides a more effective scheme to identify dynamic fMRI responses using customized macro-functions and a common neuroimage analysis software in the MRI system. Also, it provides immediate troubleshooting feasibility and a real-time biofeedback stimulation paradigm for brain functional studies in animals.

Animal brain functional mapping can benefit from the real-time functional magnetic resonance imaging (fMRI) experimental set-up. Using the latest software implemented in the animal MRI system, we established a real-time monitoring platform for small animal fMRI.

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a ...

Endovascular Perforation Model for Subarachnoid Hemorrhage Combined with Magnetic Resonance Imaging (MRI)

The endovascular filament perforation model to mimic subarachnoid hemorrhage (SAH) is a commonly used model - however, the technique can cause a high mortality rate as well as an uncontrollable volume of SAH and other intracranial complications such as stroke or intracranial hemorrhage. In this protocol, a standardized SAH mouse model is presented, induced by endovascular filament perforation, combined with magnetic resonance imaging (MRI) 24 h after operation to ensure the correct bleeding site and exclude other relevant intracranial pathologies. Briefly, C57BL/6J mice are anesthetized with an intraperitoneal ketamine/xylazine (70 mg/16 mg/kg body weight) injection and placed in a supine position. After midline neck incision, the common carotid artery (CCA) and carotid bifurcation are exposed, and a 5-0 non-absorbable monofilament polypropylene suture is inserted in a retrograde fashion into the external carotid artery (ECA) and advanced into the common carotid artery. Then, the filament is invaginated into the internal carotid artery (ICA) and pushed forward to perforate the anterior cerebral artery (ACA). After recovery from surgery, mice undergo a 7.0 T MRI 24 h later. The volume of bleeding can be quantified and graded via postoperative MRI, enabling a robust experimental SAH group with the option to perform further subgroup analyses based on blood quantity.

Endovascular Perforation Model for Subarachnoid Hemorrhage Combined with Magnetic Resonance Imaging MRI

Here we present a standardized SAH mouse model, induced by endovascular filament perforation, combined with magnetic resonance imaging (MRI) 24 h after operation to ensure the correct bleeding site and exclude other relevant intracranial pathologies.

The endovascular filament perforation model to mimic subarachnoid hemorrhage (SAH) is a commonly used model - however, the technique can cause a high ...