Fig. 1 - Above a wrapped-duster and below a free-cluster microelectrode bundle. Each wire is 50 u diameter tungsten, etched to a 1 u tip and insulated with Isonel 31. Scale line: 1 cm.
ELWIN MARG AND JOHN E. ADAMS
School of Optometry, University of California, Berkeley, Calif., and Division of Neurological Surgery, University of California Medical Center San Francisco. Calif. (U.S.A.)
This investigation was supported by a grant from theNational Science Foundation.
(Accepted for publication: February 23, 1967)
Our attempts to use multiple indwelling micro-electrodes in animals, preparatory to their use in experimental epilepsy surgery, have demonstrated that a free-cluster electrode bundle, by which arrays of micro-electrodes can be implanted, causes a minimum of disruption of the brain.
In general, a probe as thin as possible, consistent with its function, is employed in neurophysiology and neurosurgery because the larger the probe the more neurons will be injured or destroyed. As a first approximation, disruption is in proportion to the maximum cross-sectional area of the probe, neglecting for the moment the results of any possible vascular injury.
Flexible, multiple macro-electrodes for implantation in the human brain have been used for more than a decade (see e.g., Dodge et al. 1953; Chapman et al. 1954; Chatrian et al. 1959) and are now commonly used. The macro-electrode bundle is inserted by a stainless steel rod which is tipped with a styles, inserted in and driving the end loop of the bundle into the brain. After the introduction, the electrode bundle remains in place as the rod is withdrawn. It is commonly observed that stable recordings of brain waves can be made only one or more days after implantation (Adams, unpublished observations; Heath and Mickle 1960).
Fig. 1 - Above a wrapped-duster and below a
free-cluster microelectrode bundle. Each wire is 50 u diameter
tungsten, etched to a 1 u tip and insulated with Isonel 31. Scale
line: 1 cm.
Fig. 2 - Ultrasonic echogram of an animal's
brain with free-cluster micro-electrode bundle inserted. Signal
at the left is the transducer; signal to the right is the aura
mater. The vertical line points to the echo signal of the
electrode bundle above (A) and to the larger signal caused by an
electrolytic bubble at one micro-tip below (B). This demonstrates
how in principle a small electric current can be used for tip
localization.
Fig. 3 - Implantable micro-drive with a
free-cluster micro-electrode bundle. The cylinder above the
bundle fits in the burr hole with the flange screwed to the skull
surface. The gear box rests above the scalp surface and the gears
are shown exposed in the view below. A flexible drive shaft
through the bandages allows a 20 u advance per turn. Cylinder
diameter: 1 cm.
ANIMAL EXPERIMENTS
We made a similar wrapped bundle, but of microelectrodes with 5 tips distributed 1 mm apart. The basic technique has been reported (Marg 1964), using Isonel 31 insulating varnish on straight tungsten wire etched to a 1 u tip. This was modified to obtain the necessary flexibility required for indwelling electrodes. Two-mil (50 u) wire with 15 coats was used and the micro-electrode was stiff enough for a small segment at a time to be advanced directly into a rabbit brain by a micro-drive, without an introducing rod. No neural spikes could be obtained from the brain with this electrode. Even when the loop at the end of the bundle was removed, only a few spikes were recorded from the most distal tip of the bundle.
Another pair of micro-electrode bundle configurations was similarly tested. One had a group of 5 micro-electrodes wrapped with all the tips clustered together (Fig. 1, above). The other consisted of a free cluster of 5 micro-tips bound together by only a short and free segment of fine plastic tubing (Fig. 1, below). The tube was initially put at the distal end and was pushed back along the electrode bundle by the surface of the brain as the electrodes penetrated the tissue. This free-cluster micro-electrode bundle was about 5 times more effective in picking up spikes than the wrapped cluster, and the spikes were larger.
From these trials it appears evident that the marked superiority of the free-cluster configuration for a microelectrode bundle is attributable to its small cross-sectional area resulting in minimum trauma in insertion. The individual micro-electrode wires of the free-cluster appear to move rather straight in the brain, especially if initially guided straight in with the aid of the small plastic tube segment. Implanted in rabbit brains, our micro-electrodes have given unit potentials for weeks.
The smaller the diameter of an electrode the less likely it will cause vascular disruption, particularly of vessels larger than capillaries. However, it would seem that with an ordinary stiff probe, a small, sharp tip is more likely to penetrate a vessel where a large, dull tip might tend to push the tough tissue of the vessel aside rather than rupture it. Even a sharp tip will not penetrate or disrupt a tough vessel if the necessary penetration force cannot be transmitted by a thin shaft. This appears to be the case with the elements of the free-cluster bundle of micro-electrodes. It was not possible to penetrate exposed major vessels in cats and rabbits even when the shaft was constrained by gelled agar, approximately the consistency of brain tissue. This advantage must be weighed against a possible bowing or buckling of the shaft which in most areas of the brain would be far less deleterious than hemorrhage from a disrupted major vessel.
In principle it is now possible, using numbers of large free-cluster micro-electrodes, to place an array of microtips throughout the brain. Even if the individual electrode wires are visible in radiograms, it would be impracticable to locate and identify each micro-tip with its lead in the 3-dimensional array because of the confusion of wires. Identification can readily be made with the aid of ultrasonic echography. If a very small negative current (less than 1 uA) is passed through the micro-electrode (by about -2 V) for 1-2 sec, a tiny hydrolytic bubble will form at the tip. (Too much bubbling - because of an order of magnitude of higher voltage or longer time - will reduce the electrical impedance of the tip - Marg and Dierssen 1965, 1966.) The tip locus is then dynamically visualized by ultrasound because of the formation of the bubble which represents an abrupt change of acoustic impedance (Fig. 2). Thus each member tip of an array can be identified and located, one at a time, by a scanning echograph such as used for determining structures in the eye, orbit and other parts of the body. The accuracy in these instruments is limited by the beam size and wave-length and is generally better than I mm in both depth and azimuth (see e.g., Baum and Greenwood 1965). The example in Fig. 2 demonstrates the use of an electrolytic bubble from the micro-electrode as an echograph signal but does not indicate the accuracy of localization. In practice, a scanning ultrasonic echograph which can be used at a burr hole similar to that used for the eye is needed but not yet available.
By removing insulation from around the tip, for example from the distal 1 mm along the shaft, the same kinds of electrodes can be used as macro-electrodes so that both kinds of tips can be had in the same bundle if desired.
NEUROSURGICAL APPLICATION
In patients, it is desirable to be able to micro-manipulate the tips for the chronic study of neural units with indwelling micro-electrodes. This can be done with an implantable micro-drive which fits in a burr hole, and is screwed to the skull (Fig. 3). It is operated through the bandages by turning a flexible stainless steel wire which, traveling to the device at the burr hole through a flexible plastic tube, turns a worm gear. A slotted guide allows linear travel of 3 mm without rotation of the bundle. The implanted device is shown in Fig. 4. With this method we have been able to obtain various single unit responses (from the striate cortex in patients) with implanted electrodes) which exhibit directionality, binocularity and small receptive fields as well as inhibition of spontaneous activity when the eyes are closed. An example of the latter phenomenon is seen in Fig. 5.
Thus arrays of micro-electrodes can be implanted, single cells can be monitored over long periods, and new units can be sought under the head bandages of patients to contribute to their diagnostic and therapeutic brain surgery.
Fig. 4 - X-ray of implanted micro-drive
with the free-cluster micro-electrode bundle. Fine curved wires
seen around it are metal sutures.
Fig. 5 - Single unit potential in the
striate cortex which showed activity when the eyes were open (A)
but inhibition when the eyes were closed (B). Changes of
luminance did not affect this response. Calibrations: 100 uV and
5 msec.
SUMMARY
The free-cluster indwelling micro-electrode bundle effectively records single neural cells in an array in the brain. Application to neurosurgery with an implantable micro-drive is described.
RESUME
MICRO-ELECTRODES MULTIPLES IMPLANTEES DANSLE CERVEAU
Le faisceau de micro-electrodes implantees libres enregistre reellement des cellules nerveuses isolees en rang dans le cerveau. Des applications a la neuro-chirurgie avec micro-conducteur implantable vent decrites.
We thank Mrs. N. Fletcher for her assistance.
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