History, Applications, and Mechanisms of Deep Brain Stimulation

JAMA neurology 02/2013; 70(2):163-71. DOI: 10.1001/2013.jamaneurol.45
Source: PubMed


Deep brain stimulation (DBS) is an effective surgical treatment for medication-refractory hypokinetic and hyperkinetic movement disorders, and it is being explored for a variety of other neurological and psychiatric diseases. Deep brain stimulation has been Food and Drug Administration-approved for essential tremor and Parkinson disease and has a humanitarian device exemption for dystonia and obsessive-compulsive disorder. Neurostimulation is the fruit of decades of both technical and scientific advances in the field of basic neuroscience and functional neurosurgery. Despite the clinical success of DBS, the therapeutic mechanism of DBS remains under debate. Our objective is to provide a comprehensive review of DBS focusing on movement disorders, including the historical evolution of the technique, applications and outcomes with an overview of the most pertinent literature, current views on mechanisms of stimulation, and description of hardware and programming techniques. We conclude with a discussion of future developments in neurostimulation.

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    • "Externally-generated electrical currents applied to the electrodes then stimulate the surrounding brain tissue and eventually alleviate the patients3 debilitating symptoms. While new applications and brain targets for DBS continue to emerge (Hariz et al., 2013), DBS of the subthalamic nucleus (STN) or globus pallidus (GP) interna have – over the past two decades (Miocinovic et al., 2013) – become well-established treatment options for movement symptoms associated with Parkinson3s disease (PD). "
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    ABSTRACT: During implantation of deep-brain stimulation (DBS) electrodes in the target structure, neurosurgeons and neurologists commonly observe a "microlesion effect" (MLE), which occurs well before initiating subthalamic DBS. This phenomenon typically leads to a transitory improvement of motor symptoms of patients suffering from Parkinson's disease (PD). Mechanisms behind MLE remain poorly understood. In this work, we exploited the notion of ranking to assess spontaneous brain activity in PD patients examined by resting-state functional magnetic resonance imaging in response to penetration of DBS electrodes in the subthalamic nucleus. In particular, we employed a hypothesis-free method, eigenvector centrality (EC), to reveal motor-communication-hubs of the highest rank and their reorganization following the surgery; providing a unique opportunity to evaluate the direct impact of disrupting the PD motor circuitry in vivo without prior assumptions. Penetration of electrodes was associated with increased EC of functional connectivity in the brainstem. Changes in connectivity were quantitatively related to motor improvement, which further emphasizes the clinical importance of the functional integrity of the brainstem. Surprisingly, MLE and DBS were associated with anatomically different EC maps despite their similar clinical benefit on motor functions. The DBS solely caused an increase in connectivity of the left premotor region suggesting separate pathophysiological mechanisms of both interventions. While the DBS acts at the cortical level suggesting compensatory activation of less affected motor regions, the MLE affects more fundamental circuitry as the dysfunctional brainstem predominates in the beginning of PD. These findings invigorate the overlooked brainstem perspective in the understanding of PD and support the current trend towards its early diagnosis.
    Full-text · Article · Dec 2015 · Clinical neuroimaging
    • "Brain stimulation as a therapeutic tool to treat disorders of the brain has become widely accepted in diseases such as Parkinson's (using deep brain stimulation (DBS)), epilepsy (using vagus nerve stimulation), and depression (mainly using noninvasive brain stimulation devices). However, the mechanisms of action are not fully understood and the discovery of stimulation treatment is either incidental or based on explorative animal experiments (George et al., 2000; Miocinovic et al., 2013). Stimulation parameters are often set by the clinician in a trial and error approach on a subject-specific basis, and it is not understood why some subjects do not respond to the stimulation or show severe side effects. "
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    ABSTRACT: Neurostimulation as a therapeutic tool has been developed and used for a range of different diseases such as Parkinson's disease, epilepsy, and migraine. However, it is not known why the efficacy of the stimulation varies dramatically across patients or why some patients suffer from severe side effects. This is largely due to the lack of mechanistic understanding of neurostimulation. Hence, theoretical computational approaches to address this issue are in demand.
    No preview · Chapter · Dec 2015
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    • "It is thought that DBS regularizes neuronal patterns preventing the transmission of pathologic bursting and oscillatory activity in the brain. This results in improved processing of the sensomotor information and alleviation of motor symptoms (Miocinovic et al., 2013). Often there is a significant reduction in the daily levodopa dose, when STN is stimulated (Benabid et al., 2009; Malhado-Chang et al., 2008). "
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    ABSTRACT: Electromyography (EMG) and acceleration (ACC) measurements are potential methods for quantifying efficacy of deep brain stimulation (DBS) treatment in Parkinson's disease (PD). The treatment efficacy depends on the settings of DBS parameters (pulse amplitude, frequency and width). This study quantified, if EMG and ACC signal features differ between different DBS settings and if DBS effect is unequal between different muscles. EMGs were measured from biceps brachii (BB) and tibialis anterior (TA) muscles of 13 PD patients. ACCs were measured from wrists. Measurements were performed during seven different settings of DBS and analyzed using methods based on spectral analysis, signal morphology and nonlinear dynamics. The results showed significant within-subject differences in the EMG signal kurtosis, correlation dimension, recurrence rate and EMG-ACC coherence between different DBS settings for BB but not for TA muscles. Correlations between EMG feature values and clinical rest tremor and rigidity scores were weak but significant. Surface EMG features differed between different DBS settings and DBS effect was unequal between upper and lower limb muscles. EMG changes pointed to previously defined optimal settings in most of patients, which should be quantified even more deeply in the upcoming studies. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Feb 2015 · Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology
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