Neuromodulation: present and emerging methods

Abstract

Neuromodulation has wide ranging potential applications in replacing impaired neural function (prosthetics), as a novel form of medical treatment (therapy), and as a tool for investigating neurons and neural function (research). Voltage and current controlled electrical neural stimulation (ENS) are methods that have already been widely applied in both neuroscience and clinical practice for neuroprosthetics. However, there are numerous alternative methods of stimulating or inhibiting neurons. This paper reviews the state-of-the-art in ENS as well as alternative neuromodulation techniques-presenting the operational concepts, technical implementation and limitations-in order to inform system design choices.

Keywords: neural modulation; neural prosthesis; neural stimulation; neuromodulation; neuroprosthetics; neurostimulation.

Figure 1

(A) The phospholipid cell membrane, ionic charges and an ion channel. (B) A typical action potential (i) stimulation causing depolarization to above threshold, (ii) Na⁺ channels open and Na⁺ enters cell, (iii) K⁺ channels are open and K⁺ leaves cell, (iv) ion pumps restore resting potential.

Figure 2

(A) A cross-section of a myelinated nerve axon stimulated using an external stimulation electrode and an equivalent circuit model. (B) An AP generation in the nerve: simulation on the Neuron platform for AP generation with axon diameter of 15 μm, L = 1.5 mm, T = 23°C, stimulus = 300 μs, stimulus current of 147 μA. Lines show the extracellular (V_e) and membrane voltage (V_m = V_i − V_e, V_i is intracellular voltage) at the nodes 1, 2, and 3 shown in (A). For more details about the electrode-electrolyte model and the nerve model which is in this case Xenopus laevis sciatic nerve see Mou et al. (2012).

Figure 3

(A) Current-Controlled Stimulation (B) Voltage-Controlled Stimulation (C) Charge-Controlled Stimulation (D) Electrode-Electrolyte Interface model [Rs is solution spreading resistance, C_dl is double layer capacitance, R_t is charge transfer resistance (Luan and Constandinou, 2012)]

Figure 4

(A) An unilluminated channelrhodopsin-2 (ChR2) ion channel and halorhodopsin (HR) ion pump are closed and inactive. (B) Once exposed to light of specific wavelength, ChR2 allows certain positive ions into the cell, and HR begins to pump chloride ions in. (C) Activation of ChR2 initiates individual action potentials, in contrast HR activation suppresses action potentials, redrawn from Boyden et al. (2005) and Chow et al. (2010).

Figure 5

Spatio-temporal resolution of various neuromodulation methods. The open circle represents non-invasive methods and the black dots invasive methods.