The authors are grateful to Dr. Rob Franklin (Blackrock Microsystems), Prof. Margitta Seeck (Division of Neurology, Geneva University Hospitals, Geneva, Switzerland), Dr. Andrea Bartoli and Prof. Karl Schaller (Division of Neurosurgery, Geneva University Hospitals, Geneva, Switzerland), and Mr. Florent Burdin and Prof. John P. Donoghue (Wyss Center for Bio and Neuroengineering, Geneva, Switzerland) for their support in preparing the present work.

The human cadaver used in this work was provided under the framework of body donations for medical education. Informed consent for body donation was obtained in writing during the lifetime of the donor. In accordance with the federal and cantonal laws, no review by an ethics committee was necessary.
Note: This protocol assumes that the persons performing the practice surgery are neurosurgeons with training and expertise in standard neurosurgical procedures, including patient positioning and he...

The formaldehyde-fixed human cadaver model and the surgical protocol described here replicate the surgical procedure of implanting microelectrode arrays into the human cerebral neocortex. Each step of the procedure, including the positioning of the microelectrode array and its insertion with the pneumatic inserter, proceed in almost the same fashion as in a real-life patient, with the exception that cerebral pulsation and circulation are absent. The critical steps in the protocol are the alignment of the microelectrode a...

Recent years have seen the development of technological solutions to the challenge of recording the activity of multiple individual neurons in the living brain1,2,3. Silicon-based microelectrode arrays perform similarly to conventional wire microelectrodes in terms of signal properties, and they can record from dozens to hundreds of neurons in a small patch of cerebral tissue4,5,6,7. Microelectrode arrays have allowed scientists to establish the correspondence between neural activity in the primary motor cortex of monkeys and arm movements8, which in turn has provided a boost to the development of brain-computer interfaces (BCIs)9.
Microelectrode arrays have been used in humans in two situations: as chronic implants to control BCIs and as semi-chronic implants to study the activity of individual neurons in patients suffering from epilepsy. Chronic implants, targeting the functional representation of the hand in primary motor cortex, have allowed patients suffering from tetraplegia to control the motion of a robotic arm or of computer cursors10,11,12,13. Semi-chronic implants, inserted together with subdural electrocorticography (ECOG) electrodes in patients with drug-resistant epilepsy who are candidates for epilepsy surgery14, allow single-unit recordings before, during and after seizures, and have begun to shed light on the activity of single neurons during and in between epileptic seizures15,16,17,18,19. Microelectrode arrays have the potential to significantly improve our understanding of how the brain functions by establishing a link between the activity of neurons, on the one hand, and the perceptions, movements and thoughts of human beings, both in health and in disease, on the other20,21.
Silicon-based microelectrode arrays are now available commercially and their use in humans has been approved by regulatory authorities in the USA in the semi-chronic epilepsy indication. However, these devices are invasive and must be inserted into the brain. The negative consequences of improper insertion technique, beyond the failure of the device to record neuronal activity, include cerebral hemorrhage and infection, with the potential for long-lasting or permanent neurological dysfunction. Although the complication rate of microelectrode array implantation is currently unknown, the rate of potentially serious complications during the implantation of intracranial electroencephalography (EEG) macroelectrodes is 1-5%22,23. Therefore, the proper implantation of microelectrode arrays requires both extensive neurosurgical skills and procedure-specific training.
The approaches available for surgeons to hone their skills with microelectrode arrays in a safe environment include non-human mammals and human cadavers. The ideal training model would faithfully reproduce the size and thickness of the human skull; the toughness and vascular ramification of the dura; the gyrification pattern, consistency and pulsation of the human brain; the presence of circulating blood and cerebrospinal fluid; and the overall positioning of the subject in an operating room (OR)-like environment. Thus, animal models need to be of a sufficient size to provide a meaningful experience to the surgeons. Large non-human primates come closest, but their use for surgical training is unsustainable both from an ethical perspective and because they are expensive. Rodents do not enter consideration because of their small size; using even cats or rabbits implies diverging significantly from an OR-like environment.
Human cadavers represent an attractive alternative. Their advantages include the life-like size and shape of the head and brain and the possibility of setting up surgical training in an OR-like environment. The most obvious departures from a realistic situation are the absence of cerebral pulsations and bleeding and the modifications in the aspect and consistence of body tissues that are specific to the technique employed for cadaver preservation24. Fresh-frozen cadavers preserve the consistency and flexibility of many organs and tissues to some extent, but they have several drawbacks: they start degrading as soon as thawing begins, so that the brain becomes too degraded for the insertion of a microelectrode array to be performed realistically, and they are a relatively rare and expensive resource. Formaldehyde-fixed cadavers, on the other hand, are more affordable and available and much more durable, at the expense of hardened tissue consistency.
Here, we establish a procedure using a formaldehyde-fixed human cadaver model to provide neurosurgical training for the implantation of a neocortical microelectrode array. Our approach allows realistic, OR-like positioning and instrumentation; performing craniotomy and durotomy and exposing the neocortical surface; attaching the electrode pedestal to the skull bone neighboring the craniotomy; and inserting the microelectrode array into the neocortex with a pneumatic impactor25. Critically, it enables surgeons to practice the precise alignment of the microelectrode array (which is connected to the electrode pedestal by a bundle of individually insulated gold wires) parallel to the neocortical surface26. Our protocol faithfully replicates the indication of microelectrode array implantation together with ECOG implantation in patients who are candidates for epilepsy surgery. The particulars of the implantation surgery are influenced significantly by the exact type of microelectrode array; here, we describe the procedure for an array that recently received regulatory approval for use in humans in the USA. The so-called Utah array comprises a 4x4 mm, 100 microelectrode grid; a transcutaneous pedestal that is attached to the external table of the skull; and a wire bundle connecting the two.

<table border="0" cellpadding="0" cellspacing="0" width="974">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:273px;">Mayfield skull clamp</td>
			<td style="width:373px;">Integra LifeSciences, Cincinnati, OH</td>
			<td style="width:161px;">A1059</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:273px;">Midas Rex MR7 system for craniotomy</td>
			<td style="width:373px;">Medtronic, Minneapolis, MN</td>
			<td style="width:161px;">EC300</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:273px;">Dura scissors</td>
			<td style="width:373px;">Sklar Surgical Instruments, West Chester, PA</td>
			<td style="width:161px;">22-2742</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:273px;">Self-tapping bone screws</td>
			<td style="width:373px;">OrthoMed Inc., Tigard, OR</td>
			<td style="width:161px;">OM SYN211806</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:273px;">Microelectrode array and pedestal</td>
			<td style="width:373px;">Blackrock Microsystems, Salt Lake City, UT</td>
			<td style="width:161px;">LB-0612</td>
			<td>Mock-up arrays are available from the manufacturer upon request</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:273px;">Pneumatic impacter</td>
			<td style="width:373px;">Blackrock Microsystems, Salt Lake City, UT</td>
			<td style="width:161px;">LB-0088</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:273px;">64-channel electrocorticography grid</td>
			<td style="width:373px;">Ad-Tech Medical Instrument Corporation, Racine, WI</td>
			<td style="width:161px;">FG64C-SP10X-0C6</td>
			<td>Optional</td>
		</tr>
	</tbody>
</table>

surgical training for the implantation of neocortical microelectrode arrays using a formaldehyde-fixed human cadaver model

This protocol describes a procedure to assist surgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain. Recent technological progress has enabled the fabrication of microelectrode arrays that allow recording the activity of multiple individual neurons in the neocortex of the human brain. These arrays have the potential to bring unique insight onto the neuronal correlates of cerebral function in health and disease. Furthermore, the identification and decoding of volitional neuronal activity opens the possibility to establish brain-computer interfaces, and thus might help restore lost neurological functions. The implantation of neocortical microelectrode arrays is an invasive procedure requiring a supra-centimetric craniotomy and the exposure of the cortical surface; thus, the procedure must be performed by an adequately trained neurosurgeon. In order to provide an opportunity for surgical training, we designed a procedure based on a human cadaver model. The use of a formaldehyde-fixed human cadaver bypasses the practical, ethical and financial difficulties of surgical practice on animals (especially non-human primates) while preserving the macroscopic structure of the head, skull, meninges and cerebral surface and allowing realistic, operating room-like positioning and instrumentation. Furthermore, the use of a human cadaver is closer to clinical daily practice than any non-human model. The major drawbacks of the cadaveric simulation are the absence of cerebral pulsation and of blood and cerebrospinal fluid circulation. We suggest that a formaldehyde-fixed human cadaver model is an adequate, practical and cost-effective approach to ensure proper surgical training before implanting microelectrode arrays in the living human neocortex.

Our protocol uses a formaldehyde-fixated human cadaver model to allow surgeons to practice the surgical procedure of implanting a microelectrode array into the cerebral neocortex in a realistic, OR-like environment. The option of performing post-mortem neuroimaging, such as head CT, will confirm the absence of any significant intracranial lesion (Figure 1A) and can help with the selection of the implantation site. Working with an entire specimen and setting up for surgery on an operating tab...

Watch this Scientific Journal Video about Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model at JoVE.com

Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model

We designed a procedure in which a formaldehyde-fixed human cadaver is used to assist neurosurgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain.

This protocol describes a procedure to assist surgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain. ...

Microelectrodes allow recording the activity of individual neurons in the living brain. Thanks to recent developments in engineering, microelectrode arrays are becoming available for use in humans. They can give access to over a hundred individual neurons in the human cerebral neocortex.So far, microelectrode arrays have been used in humans in two circumstances. As chronic implants to control brain-computer interfaces, and as temporary implants to investigate the neural underpinnings of epilepsy in patients undergoing assessment with intracranial EEG. Microelectrode arrays are invasive devices, and their implantation requires opening the skull and meninges, and inserting the array into the cortex.Therefore, the implantation of microelectrode arrays in humans must be performed by a neurosurgeon. In addition to expertise with standard neurosurgical tools and techniques, the surgeon should be trained in anesthetic procedure of microelectrode array implantation. We designed the training procedure using a formaldehyde-fixed human cadaver.Our goals were to provide surgeons an operating room-like environment, realistic anatomy, and the opportunity to practice and rehearse the critical steps of the procedure. The protocol shown here specifically applies to the Utah array. This device comprises of 4x4-mm array of 100 silicon-based microelectrodes, a bundle of 100 individually isolated gold wires, and a transcutaneous titanium pedestal that connects to the computer recording the neural signals.The present tutorial video reviews the steps of the operative procedure starting with set up, exposing the cortical surface, fixing the pedestal, implanting the microelectrode array itself, positioning an electrocorticography or ECOG grid, and closing the craniotomy. Select a specimen with no history of disease or injury to the head, skull, and brain. If available, a postmortem head CT scan will ensure that there is no significant intracranial lesion.Fix the head in the skull clamp, and cover with surgical drapes. Incise and recline the scalp and the temporalis muscle. Perform a large square craniotomy, for instance, 5x5 centimeters.Remove the bone flap and expose the dura mater. Reserve the bone flap. Open the dura mater on three sides of the craniotomy.Recline it, and expose the arachnoid membrane and the surface of the cerebral neocortex. The first step in fixing the pedestal is to select a cortical gyrus where the microelectrode array will be implanted. The surface of the gyrus must be approximately flat so that the microelectrode array will lie flush with it when inserted.And there must be no visible blood vessel coursing on the cortical surface where the microelectrode array is to be inserted. Then, select a site for the fixation of the pedestal on the superior edge of the craniotomy close to the skin incision. Allow enough slack for the wire bundle so that the microelectrode array can reach the target gyrus.Use bone screws to screw the pedestal onto the external table of the skull bone next to the craniotomy. Throughout the procedure, it is critical to always ensure that the microelectrode array does not touch anything, as it may be damaged or could lacerate the neocortical surface. Hold the wire bundle close to the microelectrode array with tweezers with plastic or rubber coated tips.Position the microelectrode array parallel to the surface of the target gyrus. Bend the wire bundle as needed for that purpose. This is a critical step.The wire bundle is somewhat stiff and does not easily conform to the surgeons wishes. Care and patience are required to obtain good alignment of the microelectrode array and cortical surface. Dog bone titanium straps can be used to secure the wire bundle to the skull bone and control its course towards the target gyrus.Now bring the holder of the pneumatic impactor into approximate alignment with the back of the microelectrode array. The millimetric screws of the pneumatic impactor holder will be used later for finer adjustments. Fix the pneumatic impactor inside its holder.Check the connections with the control box, and then turn on the control box. Now, use the millimetric screws to bring the impactor in close alignment with the back of the microelectrode array. Then, use the impactor to apply a tack to the back of the microelectrode array and push it into the cortical surface.Check that the microelectrode array is flush with the cortical surface. Optionally, position a subdural electrocortical refragrade over the exposed cortical surface. Secure it by suturing it to the dura mater.The microelectrode array will be covered by the ECOG grade. Reposition the dura mater over the exposed cortical surface and suture it. Reposition the bone flap.Secure it with dog bone titanium straps. Make sure that the wire bundle of the microelectrode array as well as the ECOG cables do not get crushed between bone edges. Reposition and suture the skin flap.Close the skin incision around the neck of the pedestal. Alternatively, the pedestal can egress the scalp through a separate stab incision made into the skin flap. We used a formaldehyde-fixed human cadaver to allow surgeons to practice the surgical procedure of implanting a microelectrode array into the human cerebral neocortex.Advantages include an operating room-like environment and realistic human anatomy, as well as the opportunity to practice key steps of the procedure including the manipulation of the microelectrode array itself, and the use of the impactor. The obvious draw backs of using a cadaver are the absence of blood and cerebral spinal fluid circulation and the absence of the cerebral pulses caused by breathing and heartbeats. To conclude, the practice of microelectrode implantation on a formaldehyde-fixed cadaver is adequate for the training of neurosurgeons.Formaldehyde-fixed cadavers are readily available and relatively inexpensive. Such a procedure bypasses the ethical and cost-related issues of training surgeons with non-human primates.

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11.2K visualizações.  Wyss Center for Bio and Neuroengineering, Geneva. Microelectrodes allow recording the activity of individual neurons in the living brain. Thanks to recent developments in engineering, microelectrode arrays are becoming available for use in humans. They can give access to over a hundred individual neurons in the human cerebral neocortex.So far, microelectrode arrays have been used in humans in two circumstances. As chronic implants to control brain-computer interfaces, and as temporary implants to investigate the neural underpinnings o...