Deep Brain Stimulation
Deep Brain Stimulation
It has become clear that the "reversible functional lesion" paradigm that inspired the development of DBS from lesion procedures is no longer adequate to describe its effects. Early theories focused on depolarization block of efferent activity and local γ-aminobutyric acid (GABA)-mediated inhibitory effects. These notions were supported by acute stimulation experiments in animals, but paired electrode recordings and other advanced techniques complicated this picture. Proposed mechanisms of DBS can be grouped into 4 main categories: 1) inhibition of the target, the classic reversible functional lesioning paradigm; 2) activation of the target; 3) combined inhibition and activation; and 4) disruption of pathological oscillations to restore rhythmic activity and synchronization, the "noisy signal hypothesis." Recent findings have mostly supported the view that therapeutic effects are related to alterations in ongoing oscillations. In PD, subthalamic nucleus (STN) field potentials have been found to exhibit abnormal phase-amplitude coupling and spike–local field potential (LFP) coupling to primary motor cortex. Furthermore, globus pallidus internus (GPi) neurons were found to entrain high-frequency stimulation at therapeutic parameters. The "modulation of brain rhythms" hypothesis will likely provide a useful framework from which to make predictions about possible therapeutic targets for DBS.
Part of the difficulty in identifying a mechanism for the physiological effect of DBS is due to the incomplete understanding of the pathophysiology of the diverse array of movement, neuropsychiatric, and cognitive disorders currently under investigation for DBS intervention. In the following sections, we discuss recent findings in DBS research, with a focus on reviewing the evolving view of DBS target circuits.
Mechanisms of DBS
It has become clear that the "reversible functional lesion" paradigm that inspired the development of DBS from lesion procedures is no longer adequate to describe its effects. Early theories focused on depolarization block of efferent activity and local γ-aminobutyric acid (GABA)-mediated inhibitory effects. These notions were supported by acute stimulation experiments in animals, but paired electrode recordings and other advanced techniques complicated this picture. Proposed mechanisms of DBS can be grouped into 4 main categories: 1) inhibition of the target, the classic reversible functional lesioning paradigm; 2) activation of the target; 3) combined inhibition and activation; and 4) disruption of pathological oscillations to restore rhythmic activity and synchronization, the "noisy signal hypothesis." Recent findings have mostly supported the view that therapeutic effects are related to alterations in ongoing oscillations. In PD, subthalamic nucleus (STN) field potentials have been found to exhibit abnormal phase-amplitude coupling and spike–local field potential (LFP) coupling to primary motor cortex. Furthermore, globus pallidus internus (GPi) neurons were found to entrain high-frequency stimulation at therapeutic parameters. The "modulation of brain rhythms" hypothesis will likely provide a useful framework from which to make predictions about possible therapeutic targets for DBS.
Part of the difficulty in identifying a mechanism for the physiological effect of DBS is due to the incomplete understanding of the pathophysiology of the diverse array of movement, neuropsychiatric, and cognitive disorders currently under investigation for DBS intervention. In the following sections, we discuss recent findings in DBS research, with a focus on reviewing the evolving view of DBS target circuits.