Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

Abstract

Summary:Chronic electrical stimulation of the brain, known as deep brain stimulation (DBS), has become a preferred surgical treatment for medication-refractory movement disorders. Despite its remarkable clinical success, the therapeutic mechanisms of DBS are still not completely understood, limiting opportunities to improve treatment efficacy and simplify selection of stimulation parameters. This review addresses three questions essential to understanding the mechanisms of DBS. 1) How does DBS affect neuronal tissue in the vicinity of the active electrode or electrodes? 2) How do these changes translate into therapeutic benefit on motor symptoms? 3) How do these effects depend on the particular site of stimulation? Early hypotheses proposed that stimulation inhibited neuronal activity at the site of stimulation, mimicking the outcome of ablative surgeries. Recent studies have challenged that view, suggesting that although somatic activity near the DBS electrode may exhibit substantial inhibition or complex modulation patterns, the output from the stimulated nucleus follows the DBS pulse train by direct axonal excitation. The intrinsic activity is thus replaced by high-frequency activity that is time-locked to the stimulus and more regular in pattern. These changes in firing pattern are thought to prevent transmission of pathologic bursting and oscillatory activity, resulting in the reduction of disease symptoms through compensatory processing of sensorimotor information. Although promising, this theory does not entirely explain why DBS improves motor symptoms at different latencies. Understanding these processes on a physiological level will be critically important if we are to reach the full potential of this powerful tool.

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“…However, growing evidence suggests that STN-DBS also causes executive inhibitory deficits and impulsive behavior under high-conflict situations [8,[44][45][46]. In fact, the therapeutic mechanisms of DBS are still not understood completely [47].…”

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“…The primary target sites vary with patients and symptoms and include the subthalamic nuclei (STN), globus pallidus pars interna (GPi) and the ventralis intermedius nucleus of thalamus (Vim). 7 ( Figure 1). …”

Organic Bioelectronic Tools for Biomedical Applications

“…Closed-loop systems, able to sense a pathological state and exert some kind of stimulation in order to balance the environment, are gaining increasing attention, primarily in applications related to neuroscience [31,32]. Miniaturized, low-power brain-computer interface microsystems enable high performance on-line signal processing and an array of chronically implantable, biocompatible and stable electrodes can be used as biointerfaces in these advanced neuronal closed-loop systems [31].…”

“…Miniaturized, low-power brain-computer interface microsystems enable high performance on-line signal processing and an array of chronically implantable, biocompatible and stable electrodes can be used as biointerfaces in these advanced neuronal closed-loop systems [31]. Cortical brain computer interfaces, used to convey precise directions of movement [33,34], show great promise for development of robotic prostheses [35,36].…”