The “Potential” of Neuromodulation (Summer Science Series Pt. 3)

The brain’s cells, or neurons, communicate through electric signals that travel down the cells’ long, wiry branches. These electric signals, called action potentials, initiate communicative chemicals (neurotransmitters) to propagate signals onto further cells. Action potentials use an electrochemical mechanism of action in which ions are exchanged across the cell membrane. Localized ion exchange elicits the propagation of ion exchange along a whole cell branch, creating electrical energy. This will initiate or inhibit neural activity depending on the direction of the gradient. Initiation will give a little push to the cascading signal, making it more likely to happen. Inhibition will make it very difficult to achieve the ion flow needed for an action potential. As these signals are the fundamental communicative mechanism of the nervous system, a sector of neurology deals with the medical intervention of these signals. This medical intervention is called neuromodulation.

Electrical stimulation is the classic Cadillac of neuromodulation, with magnetic stimulation piggybacking on electric with very similar implementation. Light stimulation, implemented through “optogenetics” is the newest and the hip-est of the bunch. Thermal stimulation modulates through manipulation of cellular heat, while use of ultrasound causes neuromodulation, though we are still early in discovering the mechanism. Chemical modulation is indirect, changing molecule concentration that in turn affects action potentials.

In this final installment of the Summer Science Series, we check out how each of these medical methods safely and efficiently implement neuromodulation.

You may recognize this excited lady’s cap as an EEG (electroencephalogram) cap. An EEG is one common form of measuring electrical neuromodulation. Electrical neuromodulation itself also uses flat metal disks (electrodes, seen above in orange) to effect action potential by introducing external electricity. It is the most heavily researched and understood method of neuromodulation because it is the most intuitive, using electrical energy to affect the brain’s electrical energy.

 

But this method is far from perfect.

Residual charge left on the electrodes can be harmful, and so there is a limit to how powerful the safe charges can be. It is awesome that this method can be non-invasive, but a larger distance between the target area and the electrode means that the electrode must emit a stronger current and must emit it not only to the target area, but also to the tissue in between the electrode and the target area. Electrodes also degrade and require powerful batteries.

Magnetic stimulation similarly creates potential gradients but does so by introducing a rapidly changing strong magnetic field. This method is also non-invasive, and does not possess any of the electrochemical dangers found in residual charges and toxic chemical products. Sadly, spatial resolution is poor and magnetic stimulation requires incredible amounts of energy. You are also introducing an eddy current, putting any nearby metal at risk of extreme heating. This is method is not compatible with pacemakers and the like.

With optogenetics (the hip new way to neuromodulate) light-sensitive proteins are genetically inserted into cells where they act as light-activated ion transporters. Researchers choose from a variety of light-sensitive proteins. Each protein has its own biochemical fingerprint, serving a specific purpose in the cell and reacting to light at a specific rate. The coolest part about optogenetics is its spatial resolution. It resolves at the cellular level which is radically unparalleled.

So far this far out method has been restricted to research labs because genetic modification presents a huge obstacle in the clinical application of optogenetics in medicine. Genetic modification is also at the DNA level and your possession of a particular type of gene does not necessarily dictate your particular traits. Learn more about optogenetics with EyeWire’s Neurotech video below:

Thermal neuromodulation is likely a result of uniform changes in the transmembrane capacitance (capacitance is a measure of thermal energy stored in the membrane in the form of ions with opposite charges interacting through the thin membrane). Thermal neuromodulation is also likely a result of non-uniform changes in different ion channels’ conductance.

During rapid localized heating, reduced membrane capacitance allows for ion flow causing action potentials. This method is a safety concern because localized heating is damaging to tissue. Slower, widespread heating would allow for a safer intervention but would reduce the high spatial resolution of this method as well.

Through ultrasound, acoustic (mechanical) stimulation can cause neuromodulation. On-off modulated ultrasound waves may cause a physical disturbance of the cytoskeleton’s ringed structure and thereafter the intracellular fluid. This physical disturbance may initiate the opening of ion channels. Or it may not.

Currently research on the mechanism for ultrasound neuromodulation is in an infantile stage. Ultrasound allows for great spatial resolution but the standing waves(wiki) could still stimulate unwanted neural tissue.

None of these methods have entirely hacked neuromodulation, which is why there are so many of them. They all have the potential to improve and they all have their assets.

References include:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097946/

http://www.theguardian.com/science/neurophilosophy/2015/may/01/action-waves-in-the-brain