ABSTRACT
INTRODUCTIONAs described in the previous chapter, deep brain stimulation (DBS) is an important neurostimulation technique for treatment of various neurologic and psychiatric disorders. In the past 20 years, the network mechanisms underlying the clinical effects of DBS have been extensively studied [1-4]. Although these studies have revealed anatomical circuits and pathways associated with pathological behaviors, the underlying mechanisms of action of DBS are not yet completely understood. Application and study of the therapeutic effects of DBS requires a fundamental understanding of the interaction principles between electric fields and the different neural elements (e.g., axons, cell bodies, etc.) affected by such fields [5]. Thus, it is necessary to understand the electrophysiological basis of electrical stimulation and its effects
on neural tissue [6, 7]. This chapter explores the principles of extracellular stimulation, neural excitability, interactions at electrode-electrolyte tissue interface, and the electrochemical properties that affect the safety and therapeutic benefits of clinical DBS. EXTRACELLULAR STIMULATION OF NEURAL TISSUE
To appreciate how electrical stimulation can lead to modulation of neural activity, it is paramount that the effects of extracellular stimulation on neural tissue are understood. Experimental and modeling data suggest that axonal and somatic activity of electrically stimulated neurons is decoupled [8, 9]. As current enters and exits the axon in response to extracellular stimulation, both excitation and inhibition can occur at different locations within the cell. In general, cathodic stimuli depolarize the cell membrane in regions proximal to the electrode and hyperpolarize surrounding regions [9]. Anodic stimuli can have the opposite effect. This can result in a paradoxical effect in which the somatic activity can be inhibited, while the synaptic output of the cell is increased [8, 10-12]. It has been suggested that the effects of DBS most likely result from direct activation of axons rather than dendrites or cell bodies [3, 12, 13]. Accordingly, clinical studies have found that the effects DBS of the ventral intermediate thalamus (VIM) and the globus pallidus internus (GPi) are likely mediated through activation of both afferent and efferent axons [14, 15]. It is thus critical that the activation principles underlying axonal activation are understood. The remainder of this section describes the distribution and propagation of extracellular currents throughout neural tissue, the underlying mechanisms of neural excitability, as well as charge transfer mechanisms between electrons and ions at the interface between stimulating electrodes and tissue medium. Electric Fields in Volume ConductorsExtracellular stimulation involves passing an electrical current through an electrode into a tissue medium. Interactions between
the applied electrical currents and the neural tissue medium generate extracellular potentials that can activate, inhibit, or modulate neuronal firing depending on the magnitude, distribution, and polarity of the extracellular stimuli. Assessing the stimulation effects on neural tissue requires a mathematical description of the resulting electric fields on the surrounding neurons [16].
