Mechanisms of Action of Deep Brain Stimulation

Publisher Summary This chapter focuses on the five mechanisms of action of deep brain simulation (DBS), which have gained widest acceptance form the scientific community. These hypothesis include depolarization block hypothesis, synaptic modulation hypothesis, synaptic depression hypothesis, neural jamming/modulation hypothesis, and synaptic facilitation hypothesis. Depolarization block hypothesis originated from the observation that the clinical effects of DBS are similar to those of a surgical lesion suggesting that this type of stimulation acts by silencing neurons of the stimulated structure. The synaptic modulation hypothesis states that DBS activates neuronal elements that are in close proximity to the stimulating electrode, which results in local synaptic inhibition via activation of axonal terminals within the stimulated nuclei that release inhibitory neurotransmitters such as GABA. The synaptic depression hypothesis is related to the synaptic modulation hypothesis and it states that a neuron that is activated by DBS is unable to sustain high frequency action on efferent targets due to depletion of terminal vesicular stores of neurotransmitters. The neural jamming or modulation hypothesis states that DBS regulates and corrects pathological activity in the basal ganglia network. Understanding the fundamental principles of neural jamming requires a detailed knowledge of neuronal ionic conductances, as well as normal firing patterns within the thalamocortical basal ganglia network. According to the synaptic facilitation hypothesis, DBS results in the release of dopamine from surviving dopaminergic neurons projecting to the basal ganglia to contribute to the therapeutic action of STN HFS in PD patients.