Whether you practice neurophysiology in surgery, in the lab, or in the clinic, you probably use electrical stimulation to activate the nervous system on a daily basis. As you probably know, cathodal stimulation works best in some applications, while anodal stimulation works best in other applications.
Armed with this knowledge, you know precisely where to place electrodes on the body, and where to plug those electrodes in - black in cathode (-) and red in anode (+). But, what's the difference? What exactly is anodal or cathodal stimulation, and why does one work better than the other in some applications?
Today I hope to answer some of those questions for you because I believe that understanding stimulus polarity is important, and it will make you a better neurophysiologist.
Before we talk about how stimulators works, it is important to have a basic understanding of how a battery works.
How a Battery Works
The correct term for what we frequently refer to as a "battery", is a "cell", but I'm going to use the word battery to keep it simple. So, a battery is a charge-separating device. It stores electric energy by separating cations and anions into two separate compartments, or terminals (Figure 1).
- Cations are positively-charged ions (+).
- Anions are negatively-charged ions (-).
If you refer to the illustration in Figure 1, you will see that one terminal of the battery contains an excess of cations (+), and this is the positive terminal (+). Because it contains cations (+), the positive (+) terminal of the battery is called the cathode (+). The other terminal of the battery contains an excess of anions (-), and this is the negative terminal (-). Because it contains anions (-), the negative (-) terminal of the battery is called the anode (-).
When the battery is connected to a load, in this case a lightbulb, the device is powered by the flow of current. Conventional Current assumes that current flows out of the positive terminal, through the circuit and into the negative terminal. This was the convention chosen during the discovery of electricity, but they were wrong! Rather, Electrical Current is what actually happens, as electrons (-) flow out of the negative terminal (anode), through the circuit and into the positive terminal (cathode).
The take-home message is that, in a battery, current flows from anode to cathode. To learn more about batteries, go here.
How an Electrical Stimulator Works
In an electrical stimulator, the flow of anions (-) and cations (+) is controlled by the mechanics of the circuitry within the stimulator. The stimulator is unique in that the cathode is the negative pole (-) because it discharges anions (-), and the anode is the positive pole (+) because it discharges cations (+). At the end of the day, that's the fundamental difference between a battery and a stimulator.
Depending on how we configure the polarity, the stimulator will discharge either cations or anions into the body part being stimulated.
In cathodal stimulation, anions (-) are discharged into the body as current flows from the cathode (-), through the tissue, and back to the anode (+).
In anodal stimulation, cations (+) are discharged into the body as current flows from the anode (+), through the tissue, and back to the cathode (-).
Now, let's imagine that we place an electrical stimulator on the surface of the skin with a nerve bundle running underneath (Figure 2). Within the nerve bundle is a single nerve fibre (axon) upon which we will focus.
At rest, the inside of a cell is more negative than the outside of a cell. This occurs because there is a slightly greater number of negative charges than positive charges inside of the cell (intracellular space), and a slightly greater number of positive charges than negative charge outside of the cell (extracellular space). Because of the electrical difference, the cell is said to be polarized - just like a magnet, one side is more positive and the other side is more negative. If the electrical gradient were suddenly reversed, the cell would be depolarized, and we might see an action potential.
Cathodal Stimulation of Peripheral Nerves
When we use the term cathodal stimulation, what we mean is that negatively-charged anions (-) flow from the cathode, into the tissue, and back to the anode (Figure 3). As the electrical current flows from cathode to anode, negative charges (anions) tend to accumulate on the outer surface of the nerve membrane as they will be repelled by the negatively-charged cathode. This makes the outside of the membrane more negative. Consequently, the inside of the membrane becomes more positive due to accumulation of positive ions on the inside. This will result in depolarization, which, if sufficient in magnitude, will result in an action potential (nerve impulse or muscle activation).
Figure 3 illustrates activation of the axon under the cathode. As a result of stimulation, an action potential is sent in both directions along the length of the nerve, starting at the cathode. Something interesting happens underneath the anode, though! All of the negative charge from the extracellular space is attracted to the anode, leaving the outside of the cell excessively electrically positive relative to the inside of the cell. The cell is thus hyperpolarized under the anode, meaning that it is very, very difficult to activate.
If you apply the information above to the median nerve SSEP (Figure 4), then you can see why the anode is always distal, and the cathode is always proximal.
What happens when you accidentally reverse your stimulating electrodes when performing an SSEP test? The difficulty that you may experience in attempting to acquire an SSEP is explained by the phenomenon of anodal blocking (Figure 3). Thus, when bipolar electrodes have tips in the same orientation as a fiber, a fiber will be depolarized under the cathode, and hyperpolarized under the anode. If the hyperpolarization is large enough, an action potential initiated under the cathode may not be able to propagate through the region of hyperpolarization. If this is the case, the action potential will propagate in only one direction. While we often talk about the phenomenon of anodal blocking, you won't see this in the clinical scenario if you use appropriate stimulation parameters. For intraoperative monitoring of SSEPs, you should be using supramaximal stimulation. The high intensity stimulus will overcome any issues that may be experience as a result of anodal blocking.
Anodal Stimulation of Peripheral Nerves
When we use the term anodal stimulation, what we mean is that cations (+) flow from the anode, into the tissue, and back to the cathode (Figure 5). When applied to the surface of a nerve, anodal current will increase the concentration of cations (+) in the extracellular space under the anode. This will result in hyperpolarization, which, as I just mentioned, puts the cell in a heightened state of rest. So, what we see in Figure 5 is that the nerve axon becomes deactivated (hyperpolarized) under the anode.
The Importance of Cell Orientation
In all of the examples described thus far, the orientation of the cell under the stimulator has been horizontal with respect to the orientation of the anode and cathode (Figures 2-5). This is usually the case when stimulating nerves in the arms and legs.
What happens when the orientation of the cell is vertical with respect to the orientation of the anode and cathode? The answer is that things usually work exactly opposite to what we just discussed regarding horizontally-oriented cells.
This becomes particularly important in the brain where pyramidal cells of the cerebral cortex are vertically-oriented with respect to the surface where we stimulate.
Anodal Stimulation of Cerebral Cortex
Electrical stimulation of cerebral cortex is used for lots of reasons, but today I'm going to focus on motor evoked potentials (MEPs). If you use electricity (as opposed to a magnet) to evoke MEPs in your clinical practice, hopefully you know the following principle:
Whether you are stimulating the scalp over motor cortex, or directly stimulating the cortical surface, MEPs are always easiest to elicit and characterize when you use anodal, monopolar, pulse-train stimulation. Things change a little with subcortical stimulation, but that's a topic for a different day.
Starting with Fritsch and Hitzig (1870), many researchers have shown that monopolar stimulation of the motor cortex is more effective with an anode, as opposed to a cathode. Also, monopolar anodal stimulation seems to activate pyramidal cells directly.
One proposed mechanism is that anodal current enters (and hyperpolarizes) dendrites at the surface of the brain, then leaves and depolarizes the axon or cell body. One way to think about this illustrated in Figure 7.
Anodal stimulation is just the injection of positively-charged ions under the electrode. Because opposites attract, negatively charged ions migrate to the the very surface of cortex under the anode. You can think of this a current sink and the consequence is hyperpolarization of the apical dendrites of the pyramidal cell. In order to compensate for this current sink, a current source is generated distally such that positively-charged ions congregate around the other end of the pyramidal cell. This results in depolarization (activation) of the cell body, the axon hillock and the initial segment of the axon, which forms the corticospinal tract.
Of course, it isn't that simple! Computational simulations paint a more complex picture. As Figure 8 illustrates, the neural response to stimulation is likely a complex pattern of depolarization and hyperpolarization throughout the neural geometry of the cell, which is dependent upon stimulation parameters and the neural positions relative to the electrode. Clearly, when the long axis of the cell is oriented vertically relative to the orientation of an anodal stimulation electrode, the computation simulation supports hyperpolarization of the apical dendrites and depolarization around the axon hillock.
It all comes down to the orientation of the cell!
Think about this... when you place your monopolar stimulating electrode over the motor cortex and deliver anodal stimulation, your lowest threshold CMAPs are from the vertically-oriented cells just below your electrode. If you do transcranial MEPs, your electrode is probably C3 or C4, right? And, the electrode are just over the hand representation of the motor homunculus. You really have to increase the intensity to get MEPs from the legs, correct? This is because those "leg" cells are deep in the interhemispheric fissure and the cells are oriented horizontal to your anodal stimulating electrode. BUT, if you switch your polarity and deliver cathodal stimulation from the same electrode, MEPs from the legs are sometimes easier to elicit and hands become more challenging. This phenomenon works best when you are stimulation around threshold intensity. You can use this to troubleshoot your MEPs. If you begin stimulating and you get MEPs from the legs/feet at lower intensity than the arms/hands, then your polarity is probably reversed.
- Fritsch GT, Hitzig E. 1870. Über die elektrische Erregbarkeit des Grosshirns. Arch Anat Physiol Med Wiss 300–32. Translation in Von Bonin G. 1960. Some papers on the cerebral cortex. Springfield (IL): Charles C Thomas.
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Note: This article was originally published by Richard Vogel in 2015 and is being republished here for the benefit of ASNM members. The contents of this post are the work of the author and do not necessarily represent the views of the ASNM.