Toward rational design of electrical stimulation strategies for epilepsy control

Abstract

Electrical stimulation is emerging as a viable alternative for patients with epilepsy whose seizures are not alleviated by drugs or surgery. Its attractions are temporal and spatial specificity of action, flexibility of waveform parameters and timing, and the perception that its effects are reversible unlike resective surgery. However, despite significant advances in our understanding of mechanisms of neural electrical stimulation, clinical electrotherapy for seizures relies heavily on empirical tuning of parameters and protocols. We highlight concurrent treatment goals with potentially conflicting design constraints that must be resolved when formulating rational strategies for epilepsy electrotherapy, namely, seizure reduction versus cognitive impairment, stimulation efficacy versus tissue safety, and mechanistic insight versus clinical pragmatism. First, treatment markers, objectives, and metrics relevant to electrical stimulation for epilepsy are discussed from a clinical perspective. Then the experimental perspective is presented, with the biophysical mechanisms and modalities of open-loop electrical stimulation, and the potential benefits of closed-loop control for epilepsy.

Figure 1. Pinwheel of rational electrotherapy

Conflicting design factors related to (1) treatment goals, (2) treatment intensity, and (3) mechanistic insight, depicted here as yin-yang interactions, that must be resolved in the formulation of a rational electrical stimulation strategy for the treatment of epilepsy.

Figure 2

Implant damage as measured by amino-cupric silver stain for neural degeneration in rat brain. Degenerating cells and cell processes appear black. Damage due to an electrode placed in right hippocampus (lower right) can be observed as far away as the left hippocampus (lower left), as well as fibers in the fimbria (upper). (Mason et al., unpublished results).

Figure 3

Some important questions relating to the potential specificity of action of electrical stimulation in the brain.