Nerve conduction study questions...

[jerrystraub]

I'm having a bit of difficulty understanding the physiology of nerve conduction studies.

 

As described, the device generates a voltage difference beneath a surface electrode which then causes depolarization of neurons deep to the electrode.

 

This allegedly causes action potentials which move proximally or distally and which are detected by another surface electrode.

 

Knowing the time and distance thus allows calculation of a conduction "velocity."

 

First, I vaguely recall being taught that the only way to reliably generate action potentials was by either physically "clamping" a nerve or by inserting a microelectrode into the nerve.

 

To me, it seems like simply applying a voltage difference to the skin surface would only cause a localized current that might, in turn, cause some superficial muscle fibers to twitch or might stimulate pain fibers if the current generated sufficient heat.

 

Can surface electrodes cause depolarization of specific neurons? Has anyone actually stuck a microelectrode into a neuron cell and measured the action potential generated by a surface electrode. My literature search skills are admittedly rusty but I couldn't find any papers that discussed anything of that sort.

 

I would be inclined to think there would be wide variability depending upon different types of neurons, their distance from the stimulus, etc -- yet most of the recordings I've seen in normal subjects so far show near identical recordings of AP amplitude and duration all along the recording path.

 

It would make sense in an EKG that the wave is consistent since it records a huge muscle sending all of its signals in a particular direction at one time. But in something like a median nerve, which is only 2 mm in diameter and generates only 1microamp of current, given the high bioimpedance of tissue and the other factors, it just seems that any recording from a surface electrode would look rather "sloppy."

 

Also, I assume that if an action potential were generated then it would also have to propogate distally/proximally as well and therefore cause some effect -- e.g. a muscle twitch if you were studying motor fibers. By the same token, an action potential traveling along a sensory fiber would continue past the proximal electrode to the brain and be perceived as touch, hot, cold, or whatever other sensory components were activated.

 

But as I understand it, neither of these two logical (to me at least) consequences occurs during a NCT.

 

Anyway, that's the current state of my ignorance. I've read a slew of articles about NCTs but they never seem to address my specific questions. Any enlightening comments would be appreciated.

 

[EdEarl]

Apparently yes, electrodes can be attached to a single neuron.

 

[CharonY]

Analysis of ion channels on single neurons is routinely carried out using patch-clamp techniques. The resolution with modern equipment allows you to isolate areas of roughly a single ion channel. These generally require the isolation of tissues or individual cells, as far as I know.

[jerrystraub]

Thanks but I think you both misunderstood my question. I already know that microelectrodes can be inserted and patchclamp techniques can be used to study action potentials in individual neurons and I basically understand how that would work.

 

What I'm trying to understand is how action potentials are generated and recorded during diagnostic nerve conduction studies where they simply apply electrodes to the skin like they use when doing an EKG.

 

It seems like the stimulating electrode would just generate a localized current deep to wherever it's placed. Any voltage gradients generated would be across the whole cell and not just across the cell's membrane and wouldn't cause any ion channels to open and, hence, wouldn't cause any depolaization leading to action potentials.

 

So I don't understand how a surface electrode can cause specific neurons to depolarize sufficiently to trigger action potentials. And if they can, then how would it "know" which neurons were being stimulated since one might presume a lot of different neurons deep to the electrode.

 

Similarly, the reording electrode has to be able to pick up very small currents -- only about 0.3 microamps for a median nerve -- from a pretty small nerve bundle -- only 2 mm diameter for the median nerve. And it has to do that to the exclusion of all the other neuron "traffic" that might be passing beneath the recording electrode.

 

I'm not an engineer and simply fail to see how the apparatus used in a clinical nerve conduction study functions. Like I said, I have read many article on the device and they allude to generating action potentials and then measuring them but I haven't found an explanation of exactly how they do that.

[CPG]

The membrane itself acts has a very high resistance (and also capacitance but let's disregard that for now). By Ohm's law, if you pass current across a resistor, you develop a voltage across that resistor. In this case, particularly across cell membranes rather than a more diffuse voltage gradient.

 

 

 

In stimulating extracellularly, there are a number of variations that can be done (anodal versus cathodal stimulation for example), which would have a different effect on WHERE a given amount of current is able to elicit an action potential. The X-axis below shows 0 as the site of stimulation and the Y-axis shows the pattern of voltage change that would be elicited from such a stimulating pulse. The graph below that helps to illustrate how the variables of current polarity and distance would affect the region in which stimulation to threshold would be achieved.

 

 

 

You may also note from the first image above that other considerations can come into play for specificity of stimulation (for example arranging stimulation so that if an axon is depolarized at one location, it is hyperpolarized at another so any action potential that is started would simply be unable to propagate.

 

Alongside that, the strength of the stimulus can be varied, and all else being equal it is generally easier to recruit large-diameter fibers than smaller-diameter fibers. It sounds like your device stimulates small fibers. Are they the only ones there, or are there also larger fibers present? My understanding is that there are ways to deal with it if there are larger fibers - for example taking advantage of the fact that their conduction velocity would be faster, and then strategically hyperpolarizing the nerve so that it interferes with their more quickly propagating action potentials, but the hyperpolarization which aborts their action potentials is gone by the time the slower-conducting action potentials of smaller-diameter fibers reach that region.

 

I don't know specifically about the device you're describing but these general principles are presumable at play somehow. Hope that helps a bit. My apologies if the diagrams I chose are too much on the engineering side...

[Ringer]

. . .

You may want to cite the sources of those images, the information you have is good and it would be unfortunate for the post to be deleted for plagiarism.

[CPG]

Thank you for the heads up, Ringer. Those images are not mine, I guess I was thinking the embedded hyperlink would show the source but I will make it clear later when I get back to my computer. Posting from my phone now so it would be tricky to cite. Thanks

 

 

Edit: I could not edit the original post, I assume because too much time has passed since it was posted, but it is reproduced below giving credit for the images where it is due. Any help from a moderator in fixing the problem would be much appreciated. I seem to have made a mess of this one!

Edited July 12, 2013 by CPG

[CPG]

The membrane itself acts has a very high resistance (and also capacitance but let's disregard that for now). By Ohm's law, if you pass current across a resistor, you develop a voltage across that resistor. In this case, particularly across cell membranes rather than a more diffuse voltage gradient.

 

 

[image from Hamish Meffin et al 2012 J. Neural Eng. 9 065005]

Available at http://iopscience.iop.org/1741-2552/9/6/065005/article

 

 

In stimulating extracellularly, there are a number of variations that can be done (anodal versus cathodal stimulation for example), which would have a different effect on WHERE a given amount of current is able to elicit an action potential. The X-axis below shows 0 as the site of stimulation and the Y-axis shows the pattern of voltage change that would be elicited from such a stimulating pulse. The graph below that helps to illustrate how the variables of current polarity and distance would affect the region in which stimulation to threshold would be achieved.

 

 

[Above images from Chapter 21 of

Bioelectromagnetism

Principles and Applications of Bioelectric and Biomagnetic Fields

Jaakko Malmivuo and Robert Plonsey

Available at http://www.bem.fi/book/21/21.htm]

 

 

You may also note from the first image above that other considerations can come into play for specificity of stimulation (for example arranging stimulation so that if an axon is depolarized at one location, it is hyperpolarized at another so any action potential that is started would simply be unable to propagate.

 

Alongside that, the strength of the stimulus can be varied, and all else being equal it is generally easier to recruit large-diameter fibers than smaller-diameter fibers. It sounds like your device stimulates small fibers. Are they the only ones there, or are there also larger fibers present? My understanding is that there are ways to deal with it if there are larger fibers - for example taking advantage of the fact that their conduction velocity would be faster, and then strategically hyperpolarizing the nerve so that it interferes with their more quickly propagating action potentials, but the hyperpolarization which aborts their action potentials is gone by the time the slower-conducting action potentials of smaller-diameter fibers reach that region.

 

I don't know specifically about the device you're describing but these general principles are presumable at play somehow. Hope that helps a bit. My apologies if the diagrams I chose are too much on the engineering side...