Book notes Neuroengineering

I learned a good amount from reading this collection of articles but it would have been better if the book were collected into a coherent whole instead of being so fragmented. Here are summaries of random parts of the book:

Passing electrical current through tissues can stimulate neurons to produce action potentials. In vitro neuron data indicates that action potential initiation occurs in the axon even when the electrode is placed the cell body or dendrites. The electrode is usually placed around 1 mm away from the cell body. Cathode and anode stimulation have different mechanisms but they both eventually lead the depolarization of axons and thus stimulate action potentials in some form. Passing axons near to the electrode may also be stimulated as well as local neurons--this is especially true of cathodic pulses and needs to be taken into account. Moreover, since the action potential is initiated in the axon and not the cell body, extracellular unit recordings of the cell body's electrical potential may not accurately reflect the neuron's action potential output.

Deep brain stimulation uses an electrode (aka, a brain pacemaker) implanted in the subthalamic nucleus to stimulate electrical activity to relieve symptoms of Parkinson's disease, pain, and other neurological disorders. One explanation for its efficay is that neurons are functionally deafferentated by the electrical stimulation, thus limiting the propagation of tremor signals without disrupting other information pathways in the brain.

Studying DBS has yielded some principles that should be true no matter where in the brain the stimulating electrode is placed. The proximate effect of DBS will be axon and dendrite fiber excitation, and it will depend upon their ability to transmit the signal. Below frequencies of ~ 50 Hz the signal should be transduced with high fidelity, but above ~ 100 Hz axons may fail to conduct the signal properly, and synapses may not be able to recycle neurotransmitters in time. This makes sense given that that's a lot of chemistry that needs to occur more than 100 times per second!

Another interesting avenue is brain-computer interfaces, which change electrophysiological signals (like an EEG rhythm or neuronal firing rate) into a real-world output. Current signal detection methods include EEG, scalp recordings, ECoG, field potentials measured by electrodes, and single units that measured the action potentials of individual neurons. In order to shift the time scale from 1-2 seconds to 2-400 ms, penetrating electrodes that record field potentials or individuals units must be used. Penentrating electrodes that stimulate individual neurons run into issues of glial scarring and general problems with respect to biocompatability, but bioelectrodes and maybe even carbon nanotubes should overcome these problems eventually. ECoG based systems which place electrodes directly below the skin have a 5 times greater magnitude than EEG as well as a wider frequency range. Because ECoG systems also avoid the biocompatability issues of single-unit microelectrodes, they probably have the greatest clinical potential.

Noninvasive sensors will probably required in order for BCIs to become more mainstream. Unfortunately, amplification and recording or spikes noninvasively is not yet possible. Possibly some subset of neurons could be modified and could then turn electrical signals into light of a given intensity so that an external optical sensor could detect it. One possibility way to accomplish this is fluorescent seminconductor quantum dots, but that possibility is only in a theoretical stage currently.

Another interesting technique that the book reviewed was optical nerve stimulation. This is the transient deposition of energy in the form of light leading to an action potential in neural tissue.  A pulsed low energy laser beam has been shown to elicit neural action potentials indistinguishable from conventional electrical approaches on rat sciatic nerves in vivo, with far superior spatial precision and no nerve trauma due to contact. The wavelength of the photon will determine the penetration depth of the simulation, the lazer spot size can be varied down to several micrometers by changing the optical fiber diameter, and the irradiation that the tissue will experience can be varied too.

Since no specific wavelength has been found that always causes stimulation to occur, a single chromophore could not be possible for the direct photochemical effects of the laser. Also in terms of the mechanism of the laser, nerve temperature has been found to increase linearly with laser radiant exposure. So the neuronal activation may be photothermally mediated. As light energy is converted to heat, it causes a temperature gradient in time and space that is relaxed after ~ 90 ms. The molecular mechanism of action has yet to be identified, but the idea that a heat gradient may cause the action potential is very interesting. Importantly, the amount of radiant exposure needed to stimulate neurons (0.3 - 0.4 J/cm^2) is below the energy level that will deal damage to histological tissue (0.8 - 1.0 J/cm^2), making this a clinically viable technique.

Transcranial magnetic stimulation of deep brain regions is also reviewed. This technique relies on an induced electrical field that depends on a time varying magentic field which is generated by rate of change of current (dI/dt) in a bank of capacitors. The coils need to be oriented to produce an E field tangent to the surface of the skull and in the preferred direction of the neurons or axons under consideration. This is another super cool technique. The limiting factor here is often that the intensity of the magnetic field necessary to stimulate the deepest brain regions might cause facial pain or contractions as well as a risk of epileptic seizures.

Most of the techniques reviewed in the book aren't as new as some might make you believe, although there has been lots of progress in recent years. DARPA grants may spur research into the field, and the book notes that the governments of Japan and France are making BCI's a national research priority as well. Generally, neuroengineering is a highly technical pursuit that has enormous implications in the long run.

Reference

Editors: DiLorenzo DJ, Bronzino JD. 2008 Neuroengineering. CRC Press, Boca Raton. Amazon Link here.