Biomaterials for MEMS

80 S. Norman and R. Bellamkonda

Figure 4.7. An ECoG electrode array located on top of the cortex but inside the skull.

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Reprinted with permission from the Journal of Neural Engineering, Leuthanrdt et al., 2004,

Vol 1, Issue 2, pp 63–71. For color reference, see page 259.

and they are constantly being improved to increase accuracy and decrease the

amount of training time needed. It has been shown in monkeys with Utah arrays

implanted over the arm representation in the premotor cortex that predictive

models about arm movement speed up processing and could allow BCI users

to perform functions more quickly than theyareabletowithtraditionalBCI

algorithms.

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Signal processing algorithms are dependent on the method of signal

acquisition to some degree; programs to process single neuron unit data will be-

have differently from programs to interpret EEG scalp recordings, which typically

consist of the summation of thousands of neurons near the cortical surface.

BCIs have a great deal of clinical promise, but they also need refinement before

they can be used in widespread clinical trials. Once developed and refined, BCIs

have the potential to allow paralyzed and locked-in patients to interact with the

world around them and improve their quality of life.

4.3 DEVICE CONCERNS AND TISSUE RESPONSE

As with any biological implant, the materials used for a MEMs neural interface

must be biologically compatible. The device should not leach toxic materials into

the organism and should not be detrimental to the health of the animal; it also

should not deteriorate over time, unless biodegradation is the goal. Most implant

materials, even if biocompatible, trigger an inflammatory response when left in the

body for extended periods of time, and the nervous system is no exception.

The initial insertion of microelectrodes into brain or spinal cord is likely to be

harsh on the tissue. It is speculated that when a probe is inserted, it tears cells

and the surrounding tissue, and this damage triggers a cascade of events that will

manifest themselves as the inflammatory response.

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The inflammatory response

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MEMS in the Nervous System 81

is divided into acute and chronic phases; during the acute phase, microglia become

activated and respond to the foreign electrode.

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It is suspected that immune cells

circulating through the blood may also enter the brain,

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possibly via breached

blood vessels. Microglia can be seen around an electrode as soon as 24 hours after

the implant.

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The acute phase lasts for approximately 1–3 weeks after insertion,

after which the chronic phase begins.

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One of the attributes of the chronic phase of inflammation is an astrocytic

sheath formed around the implant (Fig. 4.8).

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Resting astrocytes form the blood

brain barrier, buffer excess potassium and neurotransmitters, and may supply

neurons with nutrients.

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When astrocytes become reactive, they can secrete com-

pounds inhibitory to neural growth, such as chondroitin sulfate proteoglycans

(CSPGs).

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Thesheathformedaroundtheelectrodegrowsinsizeforabout

6 weeks and then becomes thinner and denser.

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Microglia are located on the

inside of this astroglial sheath;

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activated microglia have been shown to release

inflammatory cytokines and reactive oxygen species (see Block and Hong for

review

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), and this constant release of compounds from activated microglia can

be neurotoxic.

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It has been shown that a region devoid of neurons appears next to

an implanted electrode.

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Thus, the neurons from which the probe is most likely

to record signals may be killed because of this chronic foreign body response. The

dense glial encapsulation may also interfere with electrical recording by forming

a high-impedance layer around the electrode,

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so several strategies have been

employed to lessen the severity of the glial response. Groups have experimented

with modifying electrode cross section, geometry, and tip shape, but none of these

parameters appears to mitigate the chronic glial response.

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Electrode coatings

have been developed to enhance neuronal attachment,

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butitisnotclearifthis

Figure 4.8. The response of rat cortical tissue 8 weeks after insertion. The green stain

marks glial fibrillary acidic protein (GFAP), a marker for astrocytes, and the red NeuN stain

marks neuron nuclei. The scale bar is 100 micrometers. Notice the astrocytes apparent

at the electrode interface, and that the neurons appear further away. Image courtesy of

George McConnell, Bellamkonda Lab, Georgia Institute of Technology. For color reference,

see page 260.

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