is most often faced with a compromise between the desire for a small-geometry tip, and a limitation in the charge per unit area (charge density) that can be safely injected into the tissue without causing damage to the electrode or the surrounding neuronal tissue. As the tip area is made smaller, the safe charge, and charge density, limit must be correspondingly reduced, albeit most often in a non-linear manner. Typically, intracortical electrodes are made with tip areas of less than 2,000 mm2, and for some studies electrodes as small as 200 mm2 have been used [40].

Despite the variations in electrode shape, length, or array composition, the basic interface between the electrode and the neuronal tissues remains that of a metal surface through which electrical charge is passed, and it is the nature of this interface that occupies the efforts of numerous research laboratories.

11.3  Charge Injection Using Intracortical Electrodes

11.3.1  The Intracortical Electrode as a Transducer

Electrical stimulation of neurons is accomplished by depolarizing the neuronal membrane through the flow of ionic current between two electrodes, and typically this is accomplished by injecting pulses of ionic current through the neuronal tissue that surrounds the electrode. Use of pulses to initiate the neuronal activation derives directly from the capacitive nature of the neuronal membrane. The fundamental function of the intracortical electrode is to act as a transducer for converting electronic current, flowing from the stimulator circuitry to the electrode, into ionic current that flows within the biological tissues. In order to elicit a neuronal response, a threshold membrane polarization must be reached, and for a specific electrode geometry this defines a threshold stimulation charge that the electrode must support for each stimulation pulse. For a metal electrode to support the threshold charge injection, suitable processes occurring at the electrode-tissue interface are required to cause the necessary charge-carrier conversion. These processes can be capacitive, or faradaic. In the former, a capacitive interface, formed by either the electrode-electrolyte double-layer, or a dielectric layer, is charged and discharged. For faradaic reactions, electrochemical reactions involve metal-specific charge species that are oxidized and reduced. In order to protect the electrode and the surrounding tissue from deterioration, these reactions must be reversible and limit the injection of reaction by-products into the tissue.

Capacitive-type electrodes [25], inject charge exclusively through capacitive charging and discharging, and therefore they are conceptually attractive, for use as intracortical electrodes, because they avoid the use of faradaic reactions. However, presently-known capacitive electrodes do not have sufficiently high charge-storage capacities to make them useful for intracortical stimulating electrodes. The use of surface-roughening, porous-material electrode coatings, and high-dielectric constant films, such as Ta2O5 or TiO2, have been investigated in an attempt to increase capacitive electrode charge capacities to the required stimulation threshold levels.

target neuronal pool. The second phase is designed to reverse the faradaic reactions that were utilized in the first phase by reversing the current in the electrode-electrolyte interface. Most often, but not exclusively, stimulation waveforms are generated by electronic current sources with the magnitude and duration of the first phase being replicated with an opposite magnitude and identically-timed pulse in the second phase. Owing to the simplicity in producing rectangular current pulses, the biphasic- balanced-constant-current rectangular stimulation waveform has become an historical standard for most neural stimulation systems [21, 22]. In order for an intracortical electrode to act as a stimulating transducer for chronic stimulation of neural tissue, the reversibility of the reactions must be assured, or else redox reaction by-products and unacceptable local pH shifts may damage the tissue and render the surrounding neuronal pool unusable [2, 9, 14, 36]. While some biological damage is unavoidable, due to mechanical damage resulting from the electrode insertion and electrical damage resulting from continuous charge injection, the damage must be self-limit- ing in order for the intracortical electrode to be a critical component for a cortical stimulation system.

11.3.2  Charge Injection Limits

Unfortunately, the total charge capacity of the reversible reactions that are available for a bare Pt intracortical electrode is often insufficient to initiate the necessary neuronal response. While Pt has been used quite successfully for heart pacers, cochlear implants, and other implanted neural stimulators, the extremely small size of intracortical electrodes limits the useable electrode charge capacity to well below the charge-per-pulse required for stimulation of cortical neurons. Despite this, it is quite easy to continue driving a Pt electrode with electronic current past the point at which the reversible reactions are exhausted, thus necessitating the recruitment of irreversible reactions. The most frequently recruited irreversible reactions are oxidation and reduction of water. From an electrochemical standpoint, water decomposition can provide an almost inexhaustible supply of charge carriers within the tissue, albeit with corrosion of metal. From a biological standpoint, decomposition of water as a means of neural stimulation is accompanied by huge local pH shifts, migration of metal ions into the tissue, and evolution of hydrogen and oxygen gasses. It is considered unacceptable to initiate water decomposition during cortical neural stimulation. Therefore, considerable research has been dedicated to understanding how to avoid the use of irreversible reactions during neural stimulation.

It is well-known that for a given electrode design, consisting of a particular metal type and geometric shape, there exists a window of polarization for which the electrode will not experience water redox reactions. This window is commonly called the “water window,” and, for many metals, is roughly within the range of +0.8 to −0.6 V with respect to a Ag|AgCl reference electrode. As long as the electrode polarization is held to a value within the water window there is a reasonable expectation that water decomposition will not occur. This should not be interpreted

to mean that all reactions occurring within the water window are safe: There is some suspicion that for many platinum electrode designs, some reactions taking place within the water window are not entirely reversible.

Understanding the conditions that drive an electrode’s polarization outside of the water window is often difficult, and for many years researchers attempted to define, a priori, the maximum charge density per stimulation pulse that a particular metal, or electrode coating, could support. This quantity became known as the maximum injectable charge density and is expressed in units of charge/area, frequently using mC/cm2. Establishment of the maximum injectable charge density for a particular electrode design is difficult due to the uncertainties about the relationship between charge injection and electrode polarization. Often, limits were defined based upon empirical in vitro studies, in which the physical condition of the electrode was examined following an extended pulsing regime [6]. In companion studies, electrodes were pulsed in vivo using predefined charge densities with post implantation histology being performed upon the surrounding tissue to examine adverse effects upon the local neurons or migration of metal ions [29]. Unfortunately, studies for particular electrode designs, using particular electrode metals or coatings, were often extrapolated to define the general charge injection limits for that same metal, or coating, type without regard to the electrode geometry. This created much confusion about how electrodes could be designed and used for chronic cortical stimulation so as to avoid both deterioration of the electrode and damage to the surrounding biological tissue.

In addition to damage that might be imparted to the surrounding tissue from the use of irreversible reactions, neurons can also be adversely affected, or even damaged, by over-excitation, even when operating an electrode within the water window. These changes in neuronal sensitivity and viability were observed through studies at the Huntington Medical Research Institutes [29]. From a functionality standpoint, over excitation of cortical neurons can produce a depression in neuronal activity and sensitivity. Once they are excessively stimulated, the neurons become less sensitive to subsequent stimulation pulses, thus shifting the firing threshold of the target neuronal pool. Depression can occur from either individual electrodes, near a small pool of neurons, being driven above the charge-induced depression level, or by ensembles of electrodes whose individual sub-depression charge injection levels summate causing distributed depression within a larger neuronal pool. In general, histological studies of depressed neurons do not show physical damage [29]. Yet, recovery of the depressed neurons can require hours, or even days, after cessation of the stimulation. Beyond the depression-induced threshold, physical damage to cortical neurons has been observed as a result of stimulation pulsing even when there is no evidence of driving the electrode beyond the water window [30]. This condition results in a much more serious impact upon the target neuronal pool since it is irreversible.

The combined effects of reaction-induced electrode or tissue damage and the stimulation-induced tissue depression or damage are hard to quantify. To date, no studies have established a priori charge injection limits for intracortical electrodes that consider both electrochemical and stimulation-induced effects. Furthermore,