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.
    Clinical neuroimaging 12/2015; 9:264-274. DOI:10.1016/j.nicl.2015.08.008 · 2.53 Impact Factor
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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.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 02/2015; DOI:10.1016/j.clinph.2015.01.021 · 3.10 Impact Factor
    • "It involves the stereotactic implantation of electrodes in neuroanatomical targets where stimulation is applied via a stimulator device implanted subcutaneously (Tye et al., 2009). DBS provides a focal electrical network modulation, affecting several brain circuits of interest for neurosurgery, neurology and psychiatry involving movement, neurosensitive, neurobehavioral , cognitive, and psychiatric disorders (Dallapiazza et al., 2014; Miocinovic et al., 2013). When compared to previous ablative neurosurgical procedures such as capsulotomy or cingulotomy, DBS is considered non-destructive, reversible, and adjustable (Greenberg et al., 2008). "
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    ABSTRACT: Despite a wide variety of therapeutic interventions for major depressive disorder (MDD), treatment resistant depression (TRD) remains to be prevalent and troublesome in clinical practice. In recent years, deep brain stimulation (DBS) has emerged as an alternative for individuals suffering from TRD not responding to combining antidepressants, multiple adjunctive strategies and electroconvulsive therapy (ECT). Although the best site for TRD-DBS is still unclear, pilot data suggests that the medial forebrain bundle (MFB) might be a key target to accomplish therapeutic efficacy in TRD patients. To explore the anatomic, electrophysiologic, neurocognitive and treatment data supporting the MFB as a target for TRD-DBS. The MFB connects multiple targets involved in motivated behavior, mood regulation and antidepressant response. Specific phenomenology associated with TRD can be linked specifically to the superolateral branch (sl) of the MFB (slMFB). TRD patients who received DBS-slMFB reported high response/remission rates with an improvement in functioning and no significant adverse outcomes in their physical health or neurocognitive performance. Discussion The slMFB is an essential component of a network of structural and functional pathways connecting different areas possibly involved in the pathogenesis of mood disorders. Therefore, the slMFB should be considered as an exciting therapeutic target for DBS therapy to achieve a sustained relief in TRD patients. There is an urgent need for clinical trials exploring DBS-slMFB in TRD. Further efforts should pursue measuring baseline pro-inflammatory cytokines, oxidative stress, and cognition as possible biomarkers of DBS-slMFB response in order to aid clinicians in better patient selection. Copyright © 2014 Elsevier Inc. All rights reserved.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2014; 58. DOI:10.1016/j.pnpbp.2014.12.003 · 3.69 Impact Factor
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