A bio-friendly and economical technique for chronic implantation of multiple microelectrode arrays

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Abstract

Many neurophysiological experiments on rodents and non-human primates involve the implantation of more than one multi-electrode array to record from many regions of the brain. So called ‘floating’ microelectrode arrays are implanted in cortical regions of interest and are coupled via a flexible cable to their connectors which are fixed to the skull by a cement cap or a titanium pedestal, such as the Cereport system, which has been approved for human use. The use of bone cement has several disadvantages including the creation of infection prone areas at the interface with the skull and surrounding skin. Alternatively, the more biocompatible Cereport has a limited carrying capacity and is far more expensive.

In this paper, we describe a new implantation technique, which combines the biocompatibility of titanium, a high carrying capacity with a minimal skull footprint, and a decreased chance of infection, all in a relatively inexpensive package. This technique utilizes an in-house fabricated ‘Nesting Platform’ (NP), mounted on a titanium headpost to hold multiple connectors above the skin, making the headpost the only transcutaneous object. The use of delrin, a durable, lightweight and easily machinable material, allows easy customization of the NP for a wide variety of floating electrodes and their connectors. The ultimate result is a longer survival time with superior neural recordings that can potentially last longer than with traditional implantation techniques.

Introduction

For the past several decades, researchers have made great strides in our understanding of the brain by utilizing chronic neural recordings taken from awake behaving animals (Dolbakyan et al., 1977, Nicolelis et al., 2003). Until recently most of these chronic implants had been conducted on rodents while primate neurophysiology had primarily been implemented using acute electrode insertion through chronically implanted recording chambers (Baker et al., 1999), allowing recording sessions of only several hours at a time on restrained animals. Today laboratories around the world are chronically implanting arrays of microelectrodes into non-human primates and even humans with good results (Donoghue et al., 2007, Hochberg et al., 2006). However, the risk of infection is still high when employing the commonly used cement ‘cap’ method of electrode/connector attachment in which quick drying acrylic is used in combination with skull screws.

The three major issues with chronic electrode implantations are (1) the long-term stability of the implant attachment to the skull, (2) prevention of infections and (3) the long-term stability of electrodes within the neural tissue. We will address the first two of these difficulties. Both the acrylic/cement cap (Carmena et al., 2003, Nicolelis et al., 1998, Dolbakyan et al., 1977) and the titanium pedestal (Fellows and Suner, 2006, Normann et al., 1999, Donoghue et al., 2007, Hochberg et al., 2006) techniques are widely used for chronic electrode implantation, but each has their own limitations. Acrylic is exothermic and also believed to be toxic during the settling period (Albrektsson and Linder, 1984) and the newer antibiotic (Gentamycin) impregnated bone cements like Palacose (Heraeus Medical GmbH, Wehrheim, Germany) have only limited anti-bacterial effectiveness, due to low surficial contact with surrounding bacteria. The alternative, a titanium pedestal like the Cereport (Blackrock Microsystems, Salt Lake City, UT), is biocompatible and interfaces well with surrounding bone (Adams et al., 2007). However the limited carrying capacity of each Cereport (up to 96 channels per device) requires multiple Cereport pedestal implantations for a larger number of electrode implants. Therefore, the Cereport option ultimately provides little decrease in skin margins or required skull real estate as the number of implanted electrodes increases.

To avoid the disadvantages of these previously mentioned methods we have designed and manufactured a novel apparatus in house. This apparatus, which consists of a ‘nesting platform’ (NP) mounted on a single titanium post, maintains the advantages of a traditional titanium Cereport while simultaneously increasing the carrying capacity by four times (4 × 96 electrode connectors) and reducing the transcutaneous cross section and cost. This design concept is very adaptable, and with appropriate changes in scale, could be used on animals of any size for any electrode coupled to its connector by a flexible wire; For instance floating cortical microelectrode arrays (as described here) or depth electrodes for thalamic/hippocampal implants (Behrens et al., 1994, Simuni et al., 2002). Finally, this attachment method is also very durable and does not require or impose any specific restrictions on animal movement. During the recording sessions, head movement restrictions can be imposed in order to prevent detachment of headstages from the connectors and prevent movement artifacts in the recordings, but is not required.

Section snippets

Nesting platform (NP) design

The goals of this project were to create an implantation technique that would allow the implantation of up to four 96-channel microelectrode arrays while maintaining a minimal skull footprint, minimal transcutaneous cross section, and would not require the use of acrylic cement. Fig. 1 shows our final design of the NP complex, a titanium headpost (model: 6-FHP-2XF, Crist Instrument Co., Inc., Hagerstown, MD) mated with an in-house fabricated NP that holds the electrode connectors above the

Results

We have implanted this single nesting platform with three 1.5 mm length microelectrode arrays in cortical areas PMd, M1, and S1 on a female Bonnet Macaque (M. radiata) weighing 4.2 kg on February 19, 2009 and she has been completely healthy to date (August 08, 2009); see recordings in Fig. 7. She was given systemic antibiotics daily up to day-10 post-implantation with no later antibiotic applications needed. This animal is our third animal with the Utah array implant, but the first one utilizing

Discussion

We demonstrate in this paper a novel technique of microelectrode array implantation that is cost-effective, bio-friendly, reusable and easy to implement in light of growing interest in the field of chronic multi-site, multichannel electrophysiological recordings. The NP design can be modified to meet the customized needs for individual research labs and with the advent of sophisticated milling and 3D printing technology can be finely tuned to a specific experimental setup. Thus the NP design

Conflict of interest statement

At the time of publication, no authors have any real or potential conflict of interest.

Acknowledgements

We would like to thank Shaohua Xu, Allison Maurice, Carol Novotney and Elizabeth Rivera for their continuous support throughout the course of the surgery and animal care. In addition we would like to thank John Chapin for allowing us the use of the EGX-300 desktop-engraver for making the NP. The work is supported by NYS Department of Health SCIRBs #C022048, National Academies Keck Futures Initiative NAFKI SP09 and SUNY Downstate Medical Center.

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