Electrical stimulation for epilepsy: experimental approaches

Abstract

Direct electrical stimulation of the brain is an increasingly popular means of treating refractory epilepsy. Although there has been moderate success in human trials, the rate of seizure freedom does not yet compare favorably to resective surgery. It therefore remains critical to advance experimental investigations aimed toward understanding brain stimulation and its utility. This article introduces the concepts necessary for understanding these experimental studies, describing recording and stimulation technology, animal models of epilepsy, and various subcortical targets of stimulation. Bidirectional and closed-loop device technologies are also highlighted, along with the challenges presented by their experimental use.

Figure 1

(A) Tetrode: Made by twisting 4 microwires around each other. Mainly used in single unit recording for spike sorting purposes.(A) & (B) Figures courtesy of Dr. Joseph Manns, Emory Univeristy (B) An example of a recording headstage: This particular setup allows multiple tetrodes to be driven into the brain tissue. The individual screws in the headstage allow the experimenter to drive the tetrodes to any depth throughout the span of the experiment. Using this type of headstage gives the flexibility of optimizing the position of tetrodes for picking up the best quality signals. (C) Microwire electrode array: Many microwires are arranged on a single shaft. Used for recording from many single units at the same time. (E) Silicone based microelectrodes: The advantage of using this type of microelectrode is the ability to integrate electronics such as multiplexers and amplifying circuits on the electrode system itself. Figure taken, with permission from reference [19] (F) PDMS based flexible microelectrodes: Flexible PDMS based microelectrodes are being researched as an alternative for recording from brain areas that are otherwise inaccessible to rigid microelectrode designs. Figure courtesy of Dr. Liang Guo, Georgia Institute of Technology (G) Strip macroelectrodes: These types of macroelectrodes are placed on the cortex most frequently in epileptic patients for the purposes of delineating the seizure onset zone. Electrical stimulations is also commonly performed with them for correlating physiological function with brain area for ensuring safe resection of brain tissue in epileptic subjects. Microelectrode wires can be incorporated into these (and grid) electrodes (e.g. between macro contacts). (G–I) Figures courtesy of AD-Tech, WI (H) Grid macroelectrodes: They have functions similar to the strip macroelectrodes but have many rows of electrodes instead of one single row. (I) Depth macroelectrodes: These are used for recording from deeper brain structures like the hippocampus or the amygdala. Hybrid macro/micro depth electrodes of various designs are also available.