Deep brain stimulation

<h2 id="clinical-usage">Clinical usage</h2>

The DBS system consists of three components: an implanted pulse generator (IPG), its leads and an extension. The IPG is a <a href="/facts/Battery_(electricity)/bqEpm4ue">battery</a>-powered neurostimulator encased in a <a href="/facts/Titanium/53ArnDoy">titanium</a> housing, which sends electrical pulses to the brain that interfere with <a href="/facts/Neural/CDxRKU2U">neural</a> <a href="/facts/Action_potential/Sz8yCRqx">activity</a> at the target site.
The leads are two coiled wires insulated in <a href="/facts/Polyurethane/qNo2KSXA">polyurethane</a> with four <a href="/facts/Platinum-iridium_alloy/6N1WVG1u">platinum-iridium</a> electrodes that allow delivery of electric charge from the battery back implanted in the chest wall. The battery pack is usually situated subcutaneously below the <a href="/facts/Clavicle/YWNjLv6s">clavicle</a> and rarely in the <a href="/facts/Human_abdomen/HcTzDFL0">abdomen</a>. The leads, in turn, are connected to the battery by an insulated extension wire which travels from the chest wall superiorly along the back of the neck below the skin, behind the ear, and finally enters the skull through a surgically made <a href="/facts/Burr_hole/q9PfraSC">burr hole</a> to terminate in the deep nuclei of the brain.<a class="footnote-ref" id="fnref:12" href="#fn:12">12</a> After surgery, battery dosage is titrated to individual symptoms, a process which requires repeat visits to a clinician for readjustment.<a class="footnote-ref" id="fnref:13" href="#fn:13">13</a>
DBS leads are placed in the brain according to the type of symptoms to be addressed. For non-Parkinsonian essential tremor, the lead is placed in either the ventrointermediate nucleus of the <a href="/facts/Human_thalamus/UHDtUStc">thalamus</a> or the <a href="/facts/Zona_incerta/Sb6dyNTY">zona incerta</a>;<a class="footnote-ref" id="fnref:14" href="#fn:14">14</a> for dystonia and symptoms associated with PD (<a href="/facts/Rigidity_(neurology)/XLnsqIDJ">rigidity</a>, <a href="/facts/Bradykinesia/szUKFDEn">bradykinesia</a>/<a href="/facts/Akinesia/szUKFDEn">akinesia</a>, and <a href="/facts/Tremor/rD6ogM7X">tremor</a>), the lead may be placed in either the <a href="/facts/Globus_pallidus_internus/A3kVyX1L">globus pallidus internus</a> or the <a href="/facts/Subthalamic_nucleus/2YJLz5rN">subthalamic nucleus</a>; for OCD and depression to the <a href="/facts/Nucleus_accumbens/2M43u5X4">nucleus accumbens</a>; for incessant pain to the posterior thalamic region or <a href="/facts/Periaqueductal_gray/D0wGcPvU">periaqueductal gray</a>; and for epilepsy treatment to the <a href="/facts/Anterior_nuclei_of_thalamus/Fcl17P1Q">anterior thalamic nucleus</a>.
All three components are surgically implanted inside the body. Lead implantation may take place under local anesthesia or under general anesthesia ("asleep DBS"), such as for dystonia. A hole about 14 mm in diameter is drilled in the skull and the probe electrode is inserted <a href="/facts/Stereotactic_surgery/h5dfFfA6">stereotactically</a>, using either frame-based or frameless stereotaxis.<a class="footnote-ref" id="fnref:15" href="#fn:15">15</a> During the awake procedure with local anesthesia, feedback from the person is used to determine the optimal placement of the permanent electrode. During the asleep procedure, intraoperative MRI guidance is used for direct visualization of brain tissue and device.<a class="footnote-ref" id="fnref:16" href="#fn:16">16</a> The installation of the IPG and extension leads occurs under general anesthesia.<a class="footnote-ref" id="fnref:17" href="#fn:17">17</a> The right side of the brain is stimulated to address symptoms on the left side of the body and vice versa.
Though not common, placement can be accompanied by <a href="/facts/Intracranial_hemorrhage/B41HwpBh">intracranial hemorrhage</a>, infection or <a href="/facts/Obstructive_hydrocephalus/HF9jQqTq">obstructive hydrocephalus</a>, which may require repositioning or a stay in the neurological <a href="/facts/Intensive_care_unit/j77VBgtt">intensive care unit</a>. Long term negative effects of the device include an increased risk of decreased mental function and <a href="/facts/Dementia/T0MRDE9I">dementia</a> beyond that typically seen with neurodegenerative disorders.
DBS is not considered to be a <a href="/facts/Disease-modifying_treatment/h3hDQPCX">disease-modifying treatment</a>, but rather one that improves symptoms.

<h3>Parkinson's disease</h3>
DBS is used to manage some of the symptoms of Parkinson's disease that cannot be adequately controlled with medications.<a class="footnote-ref" id="fnref:18" href="#fn:18">18</a><a class="footnote-ref" id="fnref:19" href="#fn:19">19</a> PD is treated by applying high-frequency (> 100 Hz) stimulation to target structures in the depth of the brain. Frequently used targets include the <a href="/facts/Subthalamic_nucleus/2YJLz5rN">subthalamic nucleus</a> (STN), internal <a href="/facts/Pallidum/QSGvBlAh">pallidum</a> (GPi) and ventrointermediate nucleus of the <a href="/facts/Thalamus/UHDtUStc">thalamus</a> (VIM).
A 2024 Danish meta-analysis found improvements, primarily in motor function, with deep brain stimulation with antiparkinsonian drugs against a variety of controls. Serious adverse events relating to hardware and perioperative complications were increased, but data were insufficient to assess the important outcome of all-cause mortality. All trials included were at high risk of bias, leading the authors to conclude that benefits may be overestimated and high-quality randomized trials with complete reporting of relevant outcomes remain urgently needed.<a class="footnote-ref" id="fnref:20" href="#fn:20">20</a>
DBS is recommended for people who have PD with motor fluctuations and tremors inadequately controlled by medication, or to those who are intolerant to medication, as long as they do not have severe neuropsychiatric problems.<a class="footnote-ref" id="fnref:21" href="#fn:21">21</a> Four areas of the brain have been treated with neural stimulators in PD, with the majority focusing on either the GPi or the STN.<a class="footnote-ref" id="fnref:22" href="#fn:22">22</a>
General differences between targets are not easy to summarize, but often include the following:

<ul><li>DBS of the GPi has been shown to reduce uncontrollable movements called <a href="/facts/Dyskinesia/2I2MdaSc">dyskinesias</a>. This may sometimes allow a patient to take adequate (additional) quantities of medications (especially <a href="/facts/Levodopa/4R7qahlh">levodopa</a>), thus leading to better control of symptoms.</li>
<li>DBS of the subthalamic nucleus has a more sudden effect on tremor (while effect on tremor in GPi is sometimes delayed). Also, studies associated STN-DBS with reductions in dopaminergic medication.</li>
<li>DBS of the VIM is more commonly done with tremor-dominant variants of PD (and <a href="/facts/Essential_tremor/bylon4jQ">essential tremor</a>).</li>
<li>Some studies suggested efficacy for DBS of the PPN in reducing freezing of gait, but results have been mixed and the target is not routinely used.</li></ul>
Selection of the correct DBS target is a complicated process. Multiple clinical characteristics are used to select the target including – identifying the most troublesome symptoms, the dose of levodopa that the patient is currently taking, the effects and side-effects of current medications and concurrent problems. Decisions are often made in multidisciplinary teams at specialized institutions.
The <a href="/facts/Pedunculopontine_nucleus/Sfumbr1V">pedunculopontine nucleus</a> has been used as an investigational target to treat <a href="/facts/Parkinsonian_gait/Rbb3cU5m">gait freezing</a>.

<h3>Essential tremor</h3>
ET is a neurological condition characterized by involuntary and rhythmic shaking and the most common movement disorder.<a class="footnote-ref" id="fnref:23" href="#fn:23">23</a> ET was the first indication to be approved for DBS (alongside Parkinsonian tremor) and before DBS had a long history of being treated with ablative brain lesioning.<a class="footnote-ref" id="fnref:24" href="#fn:24">24</a> Already in the first publication on the matter by the team of <a href="/facts/Alim_Louis_Benabid/UTfuzYka">Alim Louis Benabid</a>, it could be shown that frequencies above 100 Hz are most effective for cessation of tremor, while lower frequencies have less effect.<a class="footnote-ref" id="fnref:25" href="#fn:25">25</a> In clinical practice, frequencies between 80 and 180 Hz are typically applied. DBS electrodes commonly target the ventrointermediate nucleus of the thalamus (VIM) or ventrally adjacent areas that have been referred to as parts of the <a href="/facts/Zona_incerta/Sb6dyNTY">zona incerta</a>, or posterior thalamic area. Recent metaanalytical evidence suggests that multiple targets along the circuitry of the cerebellothalamic pathway (also referred to as the dentatorubrothalamic or dentatothalamic tract) are similarly effective, i.e. modulating the cerebellar inflows into the thalamus may be key for therapeutic efficacy,<a class="footnote-ref" id="fnref:26" href="#fn:26">26</a><a class="footnote-ref" id="fnref:27" href="#fn:27">27</a> for a review see.<a class="footnote-ref" id="fnref:28" href="#fn:28">28</a> Despite its success, DBS for ET is not without side effects, which can include speech difficulties and paresthesia. Similar if not the same surgical targets have been applied to treat ET using surgical lesioning in both historical but also modern context, for instance using <a href="/facts/HIFU/q4GtngEM">MR-guided Focused Ultrasound</a>, <a href="/facts/Radiosurgery/kuWjLoph">Gamma-Knife Radiosurgery</a> or conventional <a href="/facts/Radiofrequency_ablation/Fgc8V6UG">radiofrequency lesioning</a>. For instance, the annual volume of <a href="/facts/MRgFUS/q4GtngEM">MRgFUS</a> thalamotomies has recently overtaken the volume of DBS cases to treat ET.<a class="footnote-ref" id="fnref:29" href="#fn:29">29</a>

<h3>Dystonia</h3>
DBS is also an established therapeutic option for individuals with <a href="/facts/Dystonia/j0jeA0XD">dystonia</a>, a <a href="/facts/Movement_disorder/v5Q28x1f">movement disorder</a> characterized by sustained or repetitive muscle contractions, resulting in abnormal postures and involuntary movements. DBS is effective in treating primary generalized dystonia, and also used for focal dystonias such as cervical dystonia and task-specific dystonias (e.g., <a href="/facts/Writer%27s_cramp/H421v2en">writer's cramp</a>). In dystonia, marked effects can be reached by targeting the GPi using high frequency DBS, with large randomized trials demonstrating improvements of ~45% and significant improvements in quality of life within the first six months of treatment.<a class="footnote-ref" id="fnref:30" href="#fn:30">30</a> Similar effects have been reported in open label trials that targeted the STN (but this target is investigational for dystonia).<a class="footnote-ref" id="fnref:31" href="#fn:31">31</a> In contrast to some symptoms in Parkinson's disease or essential tremor, improvements in dystonia are often described to appear over weeks to months. This delayed response is thought to reflect the complexity of motor circuits involved in dystonia and the long-term plastic changes required for symptom relief. Despite the slower onset, many patients experience lasting and meaningful reductions in dystonia-related disability. DBS for dystonia is generally considered safe, but like all neuromodulation therapies, it comes with potential risks, including infection, hardware complications, or stimulation-related side effects such as speech difficulties. Ongoing research aims to optimize DBS targeting and stimulation settings to enhance outcomes for individuals with different types of dystonia. Recent large-scale mapping efforts have suggested slightly different optimal target sites for various forms of dystonia, such as generalized vs. cervical<a class="footnote-ref" id="fnref:32" href="#fn:32">32</a> or appendicular vs. axial<a class="footnote-ref" id="fnref:33" href="#fn:33">33</a> phenotypes of the disorder, potentially due to differing parts of the motor system being involved in different forms. In an attempt to develop physiomarkers that could guide <a href="/facts/Adaptive_deep_brain_stimulation/e5TkSxgc">adaptive forms of deep brain stimulation</a>, researchers have identified elevated synchrony in the theta band to be associated with symptom severity, which was found maximally expressed at optimal stimulation sites within the GPi.<a class="footnote-ref" id="fnref:34" href="#fn:34">34</a><a class="footnote-ref" id="fnref:35" href="#fn:35">35</a>

<h3>Obsessive-compulsive disorder</h3>
DBS for OCD,<a class="footnote-ref" id="fnref:36" href="#fn:36">36</a> Tourette's Syndrome,<a class="footnote-ref" id="fnref:37" href="#fn:37">37</a> and dystonia were first completed in 1999.<a class="footnote-ref" id="fnref:38" href="#fn:38">38</a>
DBS for OCD received a humanitarian device exemption from the FDA in 2009.<a class="footnote-ref" id="fnref:39" href="#fn:39">39</a> In Europe, the CE Mark for DBS for OCD was active from 2009 to 2022 but not renewed thereafter due to a lack of coverage by government health agencies.<a class="footnote-ref" id="fnref:40" href="#fn:40">40</a><a class="footnote-ref" id="fnref:41" href="#fn:41">41</a>

<h3>Epilepsy</h3>
As many as 36.3% of epilepsy patients are drug-resistant, i.e. may not be sufficiently treated with medication alone.<a class="footnote-ref" id="fnref:42" href="#fn:42">42</a> These patients are at risk for significant morbidity and mortality including <a href="/facts/Sudden_unexpected_death_in_epilepsy/9dRG5Htf">sudden unexpected death in epilepsy</a> (SUDEP).<a class="footnote-ref" id="fnref:43" href="#fn:43">43</a> If a seizure focus (i.e. seizure onset zone) can be determined (using <a href="/facts/Magnetic_resonance_imaging/Vh9yG9qq">MRI</a> and/or invasive <a href="/facts/Stereoelectroencephalography/vvl6YMbr">stereo-EEG recordings</a>) resective brain surgery that involves removing brain tissue with the ictal focus is generally preferred, since this may potentially lead to a curative outcome (i.e. a state where no seizures happen anymore). In cases where resective surgery is not an option, other neurosurgical options such as <a href="/facts/Responsive_neurostimulation_device/VcP1wQ96">responsive neurostimulation</a> (RNS), DBS, or <a href="/facts/Vagus_nerve_stimulation/U6UTTQ1z">vagus nerve stimulation</a> may be considered.<a class="footnote-ref" id="fnref:44" href="#fn:44">44</a> While RNS is a method that includes brain sensing and brain stimulation, i.e. represents a form of <a href="/facts/Adaptive_deep_brain_stimulation/e5TkSxgc">adaptive deep brain stimulation</a>, classical forms of DBS are also applied, typically at the standard 130 Hz frequency. The <a href="/facts/Anterior_nuclei_of_thalamus/Fcl17P1Q">anterior nucleus of the thalamus</a> (ANT) is the most commonly targeted area in DBS for epilepsy and the only FDA approved target site (see above). This multicenter, randomized, controlled SANTE trial (Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy) demonstrated that DBS targeting the ANT significantly reduced seizure frequency in patients with medically refractory epilepsy. Over time, patients experienced sustained seizure reductions, with some achieving more than a 50% decrease in seizures. The SANTE trial has been a pivotal study, leading to the approval of ANT-DBS for epilepsy in many countries. This region plays a key role in the network of structures that propagate seizure activity.
Beyond the ANT, several other brain regions have been explored as potential DBS targets for epilepsy. These include:

<ul><li>Centromedian nucleus (CM): Located in the thalamus, CM-DBS has been used in some cases of generalized epilepsy, including <a href="/facts/Lennox%E2%80%93Gastaut_syndrome/1RzQjdxj">Lennox-Gastaut</a> syndrome. It targets the thalamocortical networks involved in seizure propagation and has been reported to help reduce seizure severity and frequency.<a class="footnote-ref" id="fnref:45" href="#fn:45">45</a></li>
<li>Hippocampus: Particularly in patients with temporal lobe epilepsy, hippocampal DBS has been investigated as an option due to its role in seizure propagation and memory function. Studies have generally shown promising results, particularly for temporal lobe seizures.<a class="footnote-ref" id="fnref:46" href="#fn:46">46</a></li>
<li>Subthalamic nucleus (STN): Commonly used in Parkinson's disease, the STN has also been explored as a target for epilepsy due to its involvement in motor control and seizure modulation. Initial studies have shown seizure reduction, especially in patients with focal epilepsy.<a class="footnote-ref" id="fnref:47" href="#fn:47">47</a></li>
<li>Cerebellum: DBS of the cerebellum has been studied as a way to influence the modulation of neural circuits involved in epilepsy, although its use remains experimental.</li></ul>
<h3>Tourette syndrome</h3>
Further information: <a href="/facts/Management_of_Tourette_syndrome/5kJwt6s2">Management of Tourette syndrome</a>
As mentioned above, the first DBS application for Tourette's Syndrome has been carried out by the team of Veerle Visser-Vandewalle in 1999.<a class="footnote-ref" id="fnref:48" href="#fn:48">48</a> Building upon the ablative lesion cases carried out by <a href="/facts/Rolf_Hassler/pYAAKM1K">Rolf Hassler</a> and colleagues,<a class="footnote-ref" id="fnref:49" href="#fn:49">49</a> Visser-Vandewalle chose the intersection between the centromedian, parafascicular and ventrooralis internus nuclei of the thalamus as her DBS target. Authors reported that, after surgery, tics disappeared and "a change in the patient's character occurred in that he had become much more kind-hearted." DBS has been used experimentally in treating adults with severe <a href="/facts/Tourette_syndrome/YRRX4Aw4">Tourette syndrome</a> who do not respond to conventional treatment. Despite widely publicized early successes, DBS remains a highly <a href="/facts/Biomedical_research/lSVBFxDJ">experimental</a> procedure for treating Tourette's, and more study is needed to determine whether long-term benefits outweigh the risks.<a class="footnote-ref" id="fnref:50" href="#fn:50">50</a><a class="footnote-ref" id="fnref:51" href="#fn:51">51</a><a class="footnote-ref" id="fnref:52" href="#fn:52">52</a><a class="footnote-ref" id="fnref:53" href="#fn:53">53</a> The procedure is well tolerated, but complications include "short battery life, abrupt symptom worsening upon cessation of stimulation, hypomanic or manic conversion, and the significant time and effort involved in optimizing stimulation parameters".<a class="footnote-ref" id="fnref:54" href="#fn:54">54</a>
The procedure is invasive and expensive and requires long-term expert care. Benefits for severe Tourette's are inconclusive, considering the less robust effects of this surgery seen in the <a href="/facts/Netherlands/y8xn5stT">Netherlands</a>. Tourette's is more common in <a href="/facts/Pediatric/hnkMfLeg">pediatric</a> populations, tending to remit in adulthood, so, in general, this would not be a recommended procedure for use on children. It may not always be obvious how to utilize DBS for a particular person because the diagnosis of Tourette's is based on a history of symptoms rather than an examination of neurological activity. Due to concern over the use of DBS in <a href="/facts/Management_of_Tourette_syndrome/5kJwt6s2">Tourette syndrome treatment</a>, the <a href="/facts/Tourette_Association_of_America/9025kRE2">Tourette Association of America</a> convened a group of experts to develop recommendations guiding the use and potential <a href="/facts/Clinical_trials/q8LMr832">clinical trials</a> of DBS for TS.<a class="footnote-ref" id="fnref:55" href="#fn:55">55</a>
Robertson reported that DBS had been used on 55 adults by 2011, remained an experimental treatment at that time, and recommended that the procedure "should only be conducted by experienced functional neurosurgeons operating in centres which also have a dedicated Tourette syndrome clinic".<a class="footnote-ref" id="fnref:56" href="#fn:56">56</a> According to Malone et al. (2006), "Only patients with severe, debilitating, and treatment-refractory illness should be considered; while those with severe <a href="/facts/Personality_disorder/SxFnlSEW">personality disorders</a> and substance-abuse problems should be excluded."<a class="footnote-ref" id="fnref:57" href="#fn:57">57</a> Du et al. (2010) say, "As an invasive therapy, DBS is currently only advisable for severely affected, treatment-refractory TS adults".<a class="footnote-ref" id="fnref:58" href="#fn:58">58</a> Singer (2011) says, "pending determination of patient selection criteria and the outcome of carefully controlled clinical trials, a cautious approach is recommended".<a class="footnote-ref" id="fnref:59" href="#fn:59">59</a> Viswanathan et al. (2012) say DBS should be used for people with "severe functional impairment that cannot be managed medically".<a class="footnote-ref" id="fnref:60" href="#fn:60">60</a>

<h3>Depression</h3>
DBS has also been under investigational use for treatment resistant depression. Beginning in the 1950s, treatment has been attempted in the <a href="/facts/Brodmann_area_25/TfJQ1Jrm">subcallosal cingulate region</a><a class="footnote-ref" id="fnref:61" href="#fn:61">61</a> and the ventral capsule/ventral striatum (VC/VS)<a class="footnote-ref" id="fnref:62" href="#fn:62">62</a> have shown mixed outcomes. <a href="/facts/Diffusion_tensor_tractography/UzsnkIJ0">diffusion-weighted imaging based tractography</a> has led to the discovery of the so-called 'depression switch',<a class="footnote-ref" id="fnref:63" href="#fn:63">63</a> the intersection of four bundles that allowed more deliberate targeting of DBS in the SCC area and improved results in additional open-label studies.<a class="footnote-ref" id="fnref:64" href="#fn:64">64</a>
Beyond the SCC and VC/VS, a third target includes the so-called 'superolateral branch' of the <a href="/facts/Medial_forebrain_bundle/yfaYrLkm">medial forebrain bundle</a> (MFB) at the anterior limb of the internal capsule,<a class="footnote-ref" id="fnref:65" href="#fn:65">65</a> taking a course within the capsule, rather than following a trans-hypothalamic route as known for the MFB proper.<a class="footnote-ref" id="fnref:66" href="#fn:66">66</a> This target site was discovered serendipitously when a patient with Parkinson's disease developed hypomania under subthalamic nucleus DBS.<a class="footnote-ref" id="fnref:67" href="#fn:67">67</a> While this is not an uncommon side-effect of STN-DBS and alternative pathomechanisms have been suggested,<a class="footnote-ref" id="fnref:68" href="#fn:68">68</a><a class="footnote-ref" id="fnref:69" href="#fn:69">69</a> the original investigators attributed the occurrence of hypomania to stimulation of a hitherto undescribed 'superolateral' branch of the MFB, which supposedly only exists in humans.<a class="footnote-ref" id="fnref:70" href="#fn:70">70</a> While anatomical descriptions as well as supposed mechanisms for this target site have been debated,<a class="footnote-ref" id="fnref:71" href="#fn:71">71</a><a class="footnote-ref" id="fnref:72" href="#fn:72">72</a> clinical effects of this DBS target in patients with TRD have been very promising and at times with sudden onset of symptom improvements in open-label studies.<a class="footnote-ref" id="fnref:73" href="#fn:73">73</a>

<h3>Chronic pain</h3>
Stimulation of the <a href="/facts/Periaqueductal_gray/D0wGcPvU">periaqueductal gray</a> and <a href="/facts/Periventricular_nucleus/zhKEY6VI">periventricular gray</a> for <a href="/facts/Pain/70E79oUn">nociceptive pain</a>, and the <a href="/facts/Internal_capsule/vceryHK0">internal capsule</a>, <a href="/facts/Ventral_posterolateral_nucleus/oCgejnrP">ventral posterolateral nucleus</a>, and <a href="/facts/Ventral_posteromedial_nucleus/SPRUuPYm">ventral posteromedial nucleus</a> for <a href="/facts/Pain/70E79oUn">neuropathic pain</a> has produced impressive results with some people, but results vary. One study<a class="footnote-ref" id="fnref:74" href="#fn:74">74</a> of 17 people with intractable cancer pain found that 13 were virtually pain-free and only four required opioid analgesics on release from hospital after the intervention. Most ultimately did resort to opioids, usually in the last few weeks of life.<a class="footnote-ref" id="fnref:75" href="#fn:75">75</a> DBS has also been applied for <a href="/facts/Phantom_limb_pain/9Eo1AlNE">phantom limb pain</a>.<a class="footnote-ref" id="fnref:76" href="#fn:76">76</a>

<h3>Other clinical applications</h3>
Results of DBS in people with dystonia, where positive effects often appear gradually over a period of weeks to months, indicate a role of functional reorganization in at least some cases.<a class="footnote-ref" id="fnref:77" href="#fn:77">77</a> The procedure has been tested for effectiveness in people with <a href="/facts/Epilepsy/wawyp56a">epilepsy</a> that is resistant to medication.<a class="footnote-ref" id="fnref:78" href="#fn:78">78</a> DBS may reduce or eliminate epileptic seizures with programmed or responsive stimulation.
DBS of the <a href="/facts/Septal_nuclei/EIafRPqD">septal areas</a> of persons with <a href="/facts/Schizophrenia/FMP4lQ57">schizophrenia</a> has resulted in enhanced alertness, cooperation, and euphoria.<a class="footnote-ref" id="fnref:79" href="#fn:79">79</a> Persons with <a href="/facts/Narcolepsy/YfQFgVbd">narcolepsy</a> and <a href="/facts/Complex-partial_seizures/N9CRg6EA">complex-partial seizures</a> also reported euphoria and sexual thoughts from self-elicited DBS of the septal nuclei.<a class="footnote-ref" id="fnref:80" href="#fn:80">80</a>
Orgasmic ecstasy was reported with the electrical stimulation of the brain with depth electrodes in the left <a href="/facts/Hippocampus/X7CqbP8X">hippocampus</a> at 3mA, and the right <a href="/facts/Hippocampus/X7CqbP8X">hippocampus</a> at 1 mA.<a class="footnote-ref" id="fnref:81" href="#fn:81">81</a>
In 2015, a group of Brazilian researchers led by neurosurgeon Erich Fonoff [pt] described a new technique that allows for simultaneous implants of electrodes called bilateral stereotactic procedure for DBS. The main benefits are less time spent on the procedure and greater accuracy.<a class="footnote-ref" id="fnref:82" href="#fn:82">82</a>
In 2016, DBS was found to improve learning and memory in a mouse model of <a href="/facts/Rett_syndrome/dIXIgILQ">Rett syndrome</a>.<a class="footnote-ref" id="fnref:83" href="#fn:83">83</a> More recent (2018) work showed, that forniceal DBS upregulates genes involved in synaptic function, cell survival, and neurogenesis,<a class="footnote-ref" id="fnref:84" href="#fn:84">84</a> making some first steps at explaining the restoration of hippocampal circuit function.

<h2 id="device-approval">Device approval</h2>
DBS is FDA approved or has FDA device exemptions for treatment of <a href="/facts/Parkinson%27s_disease/xpekKj6x">Parkinson's disease</a>, <a href="/facts/Dystonia/j0jeA0XD">dystonia</a>, <a href="/facts/Essential_tremor/bylon4jQ">essential tremor</a>, <a href="/facts/Obsessive-compulsive_disorder/bIhDh4dz">obsessive-compulsive disorder</a> and <a href="/facts/Epilepsy/wawyp56a">epilepsy</a>. In Europe, beyond these indications, a CE mark exists for treatment of Alzheimer's disease. There was a past device exemption for OCD as well but this has not been renewed.<a class="footnote-ref" id="fnref:85" href="#fn:85">85</a> All other indications are considered investigational, i.e. carried out within medical studies under IRB approval.
The table below summarizes the history of FDA approval for DBS since creation of the device.

<table><tbody><tr><th>Indication</th><th>Approval date</th><th>Details</th><th>DBS target</th><th>Evidence</th><th>Source</th></tr><tr><td>Essential tremor (or Parkinsonian tremor)</td><td>July 31, 1997</td><td>The FDA approved DBS for the suppression of tremor in the upper extremity in patients with essential tremor.</td><td>Ventral intermediate nucleus of the thalamus (VIM)</td><td>The approval was based on clinical trials showing significant tremor reduction with thalamic DBS in patients with essential tremor, demonstrating long-term efficacy and safety. The key study is.<a class="footnote-ref" id="fnref:86" href="#fn:86">86</a></td><td><a href="https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P960009">FDA</a></td></tr><tr><td>Parkinson's disease</td><td>January 14, 2002</td><td>Approved for advanced Parkinson's disease symptoms not adequately controlled by medications.</td><td>Subthalamic nucleus (STN) or internal globus pallidus (GPi)</td><td>The key trial that led to approval is.<a class="footnote-ref" id="fnref:87" href="#fn:87">87</a> Further large-scale randomized controlled trials such as,<a class="footnote-ref" id="fnref:88" href="#fn:88">88</a> demonstrated the superiority of DBS in the subthalamic nucleus compared to best medical therapy, improving motor function and quality of life.</td><td><a href="https://www.accessdata.fda.gov/cdrh_docs/pdf/P960009S007a.pdf">FDA</a></td></tr><tr><td>Dystonia</td><td>April 15, 2003</td><td>Granted under a Humanitarian Device Exemption (HDE) for the treatment of chronic, intractable primary dystonia, including generalized and segmental dystonia, hemidystonia, and cervical dystonia in patients seven years of age or above.</td><td>Internal globus pallidus (GPi)</td><td>The key evidence came from smaller clinical trials under the Humanitarian Device Exemption, where DBS significantly improved motor function in patients with primary dystonia. Prominent trials include.<a class="footnote-ref" id="fnref:89" href="#fn:89">89</a><a class="footnote-ref" id="fnref:90" href="#fn:90">90</a></td><td><a href="https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfhde/hde.cfm?id=H020007">FDA</a></td></tr><tr><td>Obsessive-compulsive disorder</td><td>February 19, 2009</td><td>Approved under HDE for adjunctive treatment of severe, treatment-resistant OCD.</td><td>Nucleus Accumbens (NAc)</td><td>Initial approval came under HDE based on evidence from smaller, open-label trials, such as,<a class="footnote-ref" id="fnref:91" href="#fn:91">91</a> showing reductions in OCD symptoms in severe cases.</td><td><a href="https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfhde/hde.cfm?id=375533">FDA</a></td></tr><tr><td>Epilepsy</td><td>April 27, 2018</td><td>Approved for bilateral stimulation of the anterior nucleus of the thalamus (ANT) as an adjunctive therapy to reduce the frequency of seizures in adults with partial-onset seizures.</td><td>Anterior nucleus of the thalamus (ANT)</td><td>The key evidence came from the SANTE trial,<a class="footnote-ref" id="fnref:92" href="#fn:92">92</a> demonstrating a significant reduction in seizure frequency in patients receiving DBS.</td><td><a href="https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P960009S219">FDA</a></td></tr></tbody></table>
<h2 id="adaptive-deep-brain-stimulation">Adaptive deep brain stimulation</h2>
Main article: <a href="/facts/Adaptive_deep_brain_stimulation/e5TkSxgc">Adaptive deep brain stimulation</a>
Adaptive or closed-loop deep brain stimulation is a technique in which a steering signal influences when, with which amplitude or at which electrode contacts the DBS system is activated. This steering signal can be a physiological sensing signal, which is typically either recorded from the same implanted electrode or a cortical electrode/<a href="/facts/Electrocorticography/j6EhFgLV">ECoG</a> strip/grid. Alternatively, signals from <a href="/facts/Wearables/lFFo7LWf">wearables</a>, that e.g. detect symptoms such as tremor, may be used to guide stimulation across time. The concept of adaptive deep brain stimulation is as old as the concept of electrical stimulation of the brain, itself, i.e. originates in the 1950s-1960s and was implemented by early pioneers such as Carl-Wilhelm Sem-Jacobsen,<a class="footnote-ref" id="fnref:93" href="#fn:93">93</a> <a href="/facts/Natalia_Bekhtereva/T78jCESd">Natalia Bechtereva</a>,<a class="footnote-ref" id="fnref:94" href="#fn:94">94</a> <a href="/facts/Jos%C3%A9_Manuel_Rodr%C3%ADguez_Delgado/S1trf3PV">José Delgado</a><a class="footnote-ref" id="fnref:95" href="#fn:95">95</a> or <a href="/facts/Robert_Galbraith_Heath/FpudLG88">Robert Heath</a>.<a class="footnote-ref" id="fnref:96" href="#fn:96">96</a> The reason these scientists came up with the concept so early was out of necessity: At the time, chronic stimulation as carried out in open-loop (conventional) DBS applications was not technically possible using fully implanted devices, since the battery technology at the time was not ready to do so.<a class="footnote-ref" id="fnref:97" href="#fn:97">97</a> With the advent of 'modern' DBS as implemented by the team of <a href="/facts/Alim_Louis_Benabid/UTfuzYka">Alim Louis Benabid</a>, for decades, chronic, open-loop DBS became the dominant application. Here, pulses are emitted to the brain tissue in a fixed frequency (often 130 Hz) without sensing brain signals or other forms of a steering signal.It took until the 2010s, after a demonstration of efficacy of aDBS in the macaque by the team of <a href="/facts/Hagai_Bergman/A0wpVzme">Hagai Bergman</a> in 2011,<a class="footnote-ref" id="fnref:98" href="#fn:98">98</a> the first in-human application of aDBS was carried out by the team of Peter Brown in 2013,<a class="footnote-ref" id="fnref:99" href="#fn:99">99</a> followed by the team of <a href="/facts/Alberto_Priori/4nQQSVNz">Alberto Priori</a> in the same year.<a class="footnote-ref" id="fnref:100" href="#fn:100">100</a> Since then, several companies, including <a href="/facts/Medtronic/dms8dHG5">Medtronic</a> and Newronika have begun developing commercial applications of closed-loop DBS.

<h2 id="adverse-effects">Adverse effects</h2>

DBS carries the risks of major surgery, with a complication rate related to the experience of the surgical team. The major complications include hemorrhage (1–2%) and infection (3–5%).<a class="footnote-ref" id="fnref:101" href="#fn:101">101</a>
The potential exists for <a href="/facts/Neuropsychiatry/YrbzeLoc">neuropsychiatric</a> side effects after DBS, including <a href="/facts/Apathy/1Vp2zGnn">apathy</a>, <a href="/facts/Hallucinations/5eUvLcnp">hallucinations</a>, <a href="/facts/Hypersexuality/xYcTCLUl">hypersexuality</a>, <a href="/facts/Cognitive_dysfunction/PAhmL2df">cognitive dysfunction</a>, <a href="/facts/Clinical_depression/l2lQeWqr">depression</a>, and <a href="/facts/Euphoria/u4cnbWC4">euphoria</a>. However, these effects may be temporary and related to (1) incorrect placement of electrodes, (2) open-loop VS closed-loop stimulation, meaning a constant stimulation or an <a href="/facts/A.I./lJGauQwX">A.I.</a> monitoring delivery system<a class="footnote-ref" id="fnref:102" href="#fn:102">102</a> and (3) calibration of the stimulator, so these side effects are potentially reversible.<a class="footnote-ref" id="fnref:103" href="#fn:103">103</a>
Because the brain can shift slightly during surgery, the electrodes can become displaced or dislodged from the specific location. This may cause more profound complications such as <a href="/facts/Personality/zdkhBU5V">personality</a> changes, but electrode misplacement is relatively easy to identify using <a href="/facts/CT_scan/NusPJ2S8">CT scan</a>. Surgery complications may also occur, such as bleeding within the brain. After surgery, swelling of the brain tissue, mild disorientation, and sleepiness are normal. After 2–4 weeks, a follow-up visit is used to remove <a href="/facts/Surgical_suture/Pk3D50by">sutures</a>, turn on the neurostimulator, and program it.
Impaired swimming skills surfaced as an unexpected risk of the procedure; several Parkinson's disease patients lost their ability to swim after receiving deep brain stimulation.<a class="footnote-ref" id="fnref:104" href="#fn:104">104</a><a class="footnote-ref" id="fnref:105" href="#fn:105">105</a>

<h2 id="mechanisms">Mechanisms</h2>
The exact mechanism of action of DBS is not known.<a class="footnote-ref" id="fnref:106" href="#fn:106">106</a> A variety of hypotheses try to explain the mechanisms of DBS:<a class="footnote-ref" id="fnref:107" href="#fn:107">107</a><a class="footnote-ref" id="fnref:108" href="#fn:108">108</a>

<ol><li>Depolarization blockade: Electrical currents block the neuronal output at or near the electrode site.</li>
<li>Synaptic inhibition: This causes an indirect regulation of the neuronal output by activating axon terminals with synaptic connections to neurons near the stimulating electrode.</li>
<li>Desynchronization of abnormal oscillatory activity of neurons</li>
<li><a href="/facts/Antidromic/YshL1SSg">Antidromic</a> activation either activating/blockading distant neurons or blockading slow axons<a class="footnote-ref" id="fnref:109" href="#fn:109">109</a></li></ol>
DBS represents an advance on previous treatments which involved <a href="/facts/Pallidotomy/mSK5HPXR">pallidotomy</a> (i.e., surgical ablation of the <a href="/facts/Globus_pallidus/QSGvBlAh">globus pallidus</a>) or <a href="/facts/Thalamotomy/9zQvzNP7">thalamotomy</a> (i.e., surgical ablation of the thalamus).<a class="footnote-ref" id="fnref:110" href="#fn:110">110</a> Instead, a thin lead with multiple electrodes is implanted in the globus pallidus, <a href="/facts/Ventral_nuclear_group/zHoS64jo">nucleus ventralis</a> intermedius thalami, or <a href="/facts/Subthalamic_nucleus/2YJLz5rN">subthalamic nucleus</a>, and electric pulses are used therapeutically. The lead from the implant is extended to the <a href="/facts/Implanted_pulse_generator/LueJbSze">neurostimulator</a> under the skin in the chest area.
Its direct effect on the physiology of brain cells and <a href="/facts/Neurotransmitters/LlpYFSU3">neurotransmitters</a> is currently debated, but by sending high-frequency electrical impulses into specific areas of the brain, it can mitigate symptoms<a class="footnote-ref" id="fnref:111" href="#fn:111">111</a> and directly diminish the side effects induced by PD medications,<a class="footnote-ref" id="fnref:112" href="#fn:112">112</a> allowing a decrease in medications, or making a medication regimen more tolerable.

<h2 id="manufacturers">Manufacturers</h2>
There are three major competitors in the current market for stimulators, <a href="/facts/Boston_Scientific/XmyKQUA5">Boston Scientific</a>, <a href="/facts/Medtronic/dms8dHG5">Medtronic</a> and <a href="/facts/Abbott_Laboratories/G0uWjHK9">Abbott</a>. Medtronic is developing a closed loop system which can be based on automatic feedback and Abbott allows remote programming.

<h2 id="see-also">See also</h2>
<ul><li><a href="/facts/Brain_implant/eaHAKydz">Brain implant</a></li>
<li><a href="/facts/Brain_stimulation_reward/Sk6U39Yq">Brain stimulation reward</a></li>
<li><a href="/facts/Electroconvulsive_therapy/n498J3Km">Electroconvulsive therapy</a></li>
<li><a href="/facts/Neuromodulation_(medicine)/2MHUQoBv">Neuromodulation (medicine)</a></li>
<li><a href="/facts/Neuroprosthetics/K38auu8M">Neuroprosthetics</a></li>
<li><a href="/facts/Neuroregeneration/2wAxXAF2">Neuroregeneration</a></li>
<li><a href="/facts/Neurotherapy/ymHxLEsS">Neurotherapy</a></li>
<li><a href="/facts/Responsive_neurostimulation_device/VcP1wQ96">Responsive neurostimulation device</a></li>
<li><a href="/facts/Transcranial_magnetic_stimulation/XFf4ED3L">Transcranial magnetic stimulation</a></li>
<li><a href="/facts/Lead-DBS/JGoQ4SNp">Lead-DBS</a></li></ul>

<h2 id="further-reading">Further reading</h2>

<ul><li>Appleby BS, Duggan PS, Regenberg A, Rabins PV (September 2007). "Psychiatric and neuropsychiatric adverse events associated with deep brain stimulation: A meta-analysis of ten years' experience". Movement Disorders. 22 (12): 1722–1728. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2Fmds.21551">10.1002/mds.21551</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17721929">17721929</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:22925963">22925963</a>.</li>
<li>Schlaepfer TE, Bewernick BH, Kayser S, Hurlemann R, Coenen VA (May 2014). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988559">"Deep brain stimulation of the human reward system for major depressionsnd – rationale, outcomes and outlook"</a>. Neuropsychopharmacology. 39 (6): 1303–1314. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2Fnpp.2014.28">10.1038/npp.2014.28</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988559">3988559</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/24513970">24513970</a>.</li>
<li>Diamond A, Shahed J, Azher S, Dat-Vuong K, Jankovic J (May 2006). "Globus pallidus deep brain stimulation in dystonia". Movement Disorders. 21 (5): 692–695. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2Fmds.20767">10.1002/mds.20767</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16342255">16342255</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:29677149">29677149</a>.</li>
<li>Richter EO, Lozano AM (2004). "Deep Brain Stimulation for Parkinson's Disease and Movement Disorders". Bioelectromagnetic Medicine. pp. 271–282. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.3109%2F9780203021651-24">10.3109/9780203021651-24</a>. <a href="/facts/ISBN_(identifier)/15AdSPa9">ISBN</a> 978-0-429-22857-5.</li></ul>

<h2 id="external-links">External links</h2>

Wikimedia Commons has media related to Deep brain stimulation.

<ul><li>Video: <a href="https://www.youtube.com/watch?v=KDjWdtDyz5I">Deep brain stimulation to treat Parkinson's disease</a></li>
<li>Video: <a href="https://www.youtube.com/watch?v=9phXvB077Dw">Deep brain stimulation therapy for Parkinson's disease</a></li>
<li><a href="http://www.madinamerica.com/2015/09/adverse-effects-perils-deep-brain-stimulation-depression/">The Perils of Deep Brain Stimulation for Depression. Author Danielle Egan. September 24, 2015.</a></li>
<li><a href="https://www.mountsinai.org/locations/center-neuromodulation/what-is/dbs/info">Treatment center for Deep Brain Stimulation of movement disorders, OCD, Tourette or depression.</a></li>
<li><a href="https://www.mountsinai.org/care/behavioral-health/services/ocd-tics/dbs">Treatment center for Deep Brain Stimulation for OCD</a></li></ul>

<h2 id="references">References</h2>

<ol>
<li id="fn:1">Kringelbach ML, Jenkinson N, Owen SL, Aziz TZ (August 2007). "Translational principles of deep brain stimulation". Nature Reviews. Neuroscience. 8 (8): 623–635. doi:10.1038/nrn2196. PMID 17637800. S2CID 147427108. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></li>
<li id="fn:2">García MR, Pearlmutter BA, Wellstead PE, Middleton RH (16 September 2013). "A slow axon antidromic blockade hypothesis for tremor reduction via deep brain stimulation". PLOS ONE. 8 (9): e73456. Bibcode:2013PLoSO...873456G. doi:10.1371/journal.pone.0073456. PMC 3774723. PMID 24066049. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774723" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774723</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></li>
<li id="fn:3">"FDA approves brain implant to help reduce Parkinson's disease and essential tremor symptoms". FDA. Retrieved May 23, 2016. The first device, Medtronic's Activa Deep Brain Stimulation Therapy System, was approved in 1997 for tremor associated with essential tremor and Parkinson's disease. <a href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm451152.htm" target="_blank">https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm451152.htm</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></li>
<li id="fn:4">Phillips S (17 June 2007). "'Brain pacemaker' for a rare disorder". NBC News. Archived from the original on April 28, 2021. <a href="https://web.archive.org/web/20210428014405/https://www.nbcnews.com/id/wbna19265007" target="_blank">https://web.archive.org/web/20210428014405/https://www.nbcnews.com/id/wbna19265007</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></li>
<li id="fn:5">"Medtronic Receives FDA Approval for Deep Brain Stimulation Therapy for Medically Refractory Epilepsy" (Press release). Medtronic. 1 May 2018. <a href="https://news.medtronic.com/2018-05-01-Medtronic-Receives-FDA-Approval-for-Deep-Brain-Stimulation-Therapy-for-Medically-Refractory-Epilepsy" target="_blank">https://news.medtronic.com/2018-05-01-Medtronic-Receives-FDA-Approval-for-Deep-Brain-Stimulation-Therapy-for-Medically-Refractory-Epilepsy</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></li>
<li id="fn:6">"FDA Approves Humanitarian Device Exemption for Deep Brain Stimulator for Severe Obsessive-Compulsive Disorder". FDA. <a href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149529.htm" target="_blank">https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149529.htm</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></li>
<li id="fn:7">Gildenberg PL (2005). "Evolution of neuromodulation". Stereotactic and Functional Neurosurgery. 83 (2–3): 71–79. doi:10.1159/000086865. PMID 16006778. S2CID 20234898. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></li>
<li id="fn:8">Kringelbach ML, Jenkinson N, Owen SL, Aziz TZ (August 2007). "Translational principles of deep brain stimulation". Nature Reviews. Neuroscience. 8 (8): 623–635. doi:10.1038/nrn2196. PMID 17637800. S2CID 147427108. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></li>
<li id="fn:9">Morris JG, Owler B, Hely MA, Fung VS (2007). "Hydrocephalus and structural lesions". Parkinson's Disease and Related Disorders, Part II. Handbook of Clinical Neurology. Vol. 84. pp. 459–478. doi:10.1016/S0072-9752(07)84055-3. ISBN 978-0-444-52893-3. OCLC 1132129865. PMID 18808964. <a href="978-0-444-52893-3" target="_blank">978-0-444-52893-3</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></li>
<li id="fn:10">Hollunder, Barbara; Ostrem, Jill L.; Sahin, Ilkem Aysu; Rajamani, Nanditha; Oxenford, Simón; Butenko, Konstantin; Neudorfer, Clemens; Reinhardt, Pablo; Zvarova, Patricia; Polosan, Mircea; Akram, Harith; Vissani, Matteo; Zhang, Chencheng; Sun, Bomin; Navratil, Pavel (March 2024). "Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation". Nature Neuroscience. 27 (3): 573–586. doi:10.1038/s41593-024-01570-1. ISSN 1097-6256. PMC 10917675. PMID 38388734. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917675" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917675</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></li>
<li id="fn:11">Grill, Warren M.; Snyder, Andrea N.; Miocinovic, Svjetlana (May 2004). "Deep brain stimulation creates an informational lesion of the stimulated nucleus". NeuroReport. 15 (7): 1137–1140. doi:10.1097/00001756-200405190-00011. ISSN 0959-4965. PMID 15129161. <a href="http://journals.lww.com/00001756-200405190-00011" target="_blank">http://journals.lww.com/00001756-200405190-00011</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></li>
<li id="fn:12">"Deep Brain Stimulation for Movement Disorders". National Institute on Neurological Disorders and Stroke. <a href="https://www.ninds.nih.gov/health-information/disorders/deep-brain-stimulation-movement-disorders" target="_blank">https://www.ninds.nih.gov/health-information/disorders/deep-brain-stimulation-movement-disorders</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></li>
<li id="fn:13">Volkmann J, Herzog J, Kopper F, Deuschl G (2002). "Introduction to the programming of deep brain stimulators". Movement Disorders. 17 (Suppl 3): S181 – S187. doi:10.1002/mds.10162. PMID 11948775. S2CID 21988668. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></li>
<li id="fn:14">Lee JY, Deogaonkar M, Rezai A (July 2007). "Deep brain stimulation of globus pallidus internus for dystonia". Parkinsonism & Related Disorders. 13 (5): 261–265. doi:10.1016/j.parkreldis.2006.07.020. PMID 17081796. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></li>
<li id="fn:15">Owen CM, Linskey ME (May 2009). "Frame-based stereotaxy in a frameless era: current capabilities, relative role, and the positive- and negative predictive values of blood through the needle". Journal of Neuro-Oncology. 93 (1): 139–149. doi:10.1007/s11060-009-9871-y. PMID 19430891. <a href="https://doi.org/10.1007%2Fs11060-009-9871-y" target="_blank">https://doi.org/10.1007%2Fs11060-009-9871-y</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></li>
<li id="fn:16">Starr PA, Martin AJ, Ostrem JL, Talke P, Levesque N, Larson PS (March 2010). "Subthalamic nucleus deep brain stimulator placement using high-field interventional magnetic resonance imaging and a skull-mounted aiming device: technique and application accuracy". Journal of Neurosurgery. 112 (3): 479–490. doi:10.3171/2009.6.JNS081161. PMC 2866526. PMID 19681683. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866526" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866526</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></li>
<li id="fn:17">"Deep Brain Stimulation for Movement Disorders". University of Pittsburgh. <a href="https://www.neurosurgery.pitt.edu/centers/epilepsy/dbs-movement-disorders" target="_blank">https://www.neurosurgery.pitt.edu/centers/epilepsy/dbs-movement-disorders</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></li>
<li id="fn:18">"Deep Brain Stimulation for Movement Disorders". National Institute on Neurological Disorders and Stroke. <a href="https://www.ninds.nih.gov/health-information/disorders/deep-brain-stimulation-movement-disorders" target="_blank">https://www.ninds.nih.gov/health-information/disorders/deep-brain-stimulation-movement-disorders</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></li>
<li id="fn:19">U.S. Department of Health and Human Services. FDA approves implanted brain stimulator to control tremors. Retrieved February 10, 2015. <a href="https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm083894.htm" target="_blank">https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm083894.htm</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></li>
<li id="fn:20">Petersen, Johanne Juul; Kamp, Caroline Barkholt; Faltermeier, Pascal; Juul, Sophie; Løkkegaard, Annemette; Gluud, Christian; Jakobsen, Janus C (2024). "Deep brain stimulation for Parkinson's disease: systematic review with meta-analysis and trial sequential analysis". BMJ Medicine. 3 (1): e000705. doi:10.1136/bmjmed-2023-000705. ISSN 2754-0413. <a href="https://doi.org/10.1136%2Fbmjmed-2023-000705" target="_blank">https://doi.org/10.1136%2Fbmjmed-2023-000705</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></li>
<li id="fn:21">Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A, et al. (February 2011). "Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues". Archives of Neurology. 68 (2): 165. doi:10.1001/archneurol.2010.260. PMC 4523130. PMID 20937936. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523130" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523130</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></li>
<li id="fn:22">Follett, Kenneth A.; Weaver, Frances M.; Stern, Matthew; Hur, Kwan; Harris, Crystal L.; Luo, Ping; Marks, William J.; Rothlind, Johannes; Sagher, Oren; Moy, Claudia; Pahwa, Rajesh; Burchiel, Kim; Hogarth, Penelope; Lai, Eugene C.; Duda, John E. (2010-06-03). "Pallidal versus Subthalamic Deep-Brain Stimulation for Parkinson's Disease". New England Journal of Medicine. 362 (22): 2077–2091. doi:10.1056/NEJMoa0907083. ISSN 0028-4793. PMID 20519680. <a href="http://www.nejm.org/doi/abs/10.1056/NEJMoa0907083" target="_blank">http://www.nejm.org/doi/abs/10.1056/NEJMoa0907083</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></li>
<li id="fn:23">"Essential Tremor: Essential Facts for Patients". www.movementdisorders.org. Retrieved 2024-09-22. <a href="https://www.movementdisorders.org/MDS/Resources/Patient-Education/Essential-Tremor.htm" target="_blank">https://www.movementdisorders.org/MDS/Resources/Patient-Education/Essential-Tremor.htm</a> <a href="#fnref:23" class="footnote-back-ref">↩</a></li>
<li id="fn:24">Neudorfer, Clemens; Kultas-Ilinsky, Kristy; Ilinsky, Igor; Paschen, Steffen; Helmers, Ann-Kristin; Cosgrove, G. Rees; Richardson, R. Mark; Horn, Andreas; Deuschl, Günther (April 2024). "The role of the motor thalamus in deep brain stimulation for essential tremor". Neurotherapeutics. 21 (3): e00313. doi:10.1016/j.neurot.2023.e00313. PMC 11103222. PMID 38195310. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103222" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103222</a> <a href="#fnref:24" class="footnote-back-ref">↩</a></li>
<li id="fn:25">Benabid, A.L.; Pollak, P.; Hoffmann, D.; Gervason, C.; Hommel, M.; Perret, J.E.; de Rougemont, J.; Gao, D.M. (February 1991). "Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus". The Lancet. 337 (8738): 403–406. doi:10.1016/0140-6736(91)91175-T. PMID 1671433. <a href="https://linkinghub.elsevier.com/retrieve/pii/014067369191175T" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/014067369191175T</a> <a href="#fnref:25" class="footnote-back-ref">↩</a></li>
<li id="fn:26">Nowacki, Andreas; Barlatey, Sabry; Al-Fatly, Bassam; Dembek, Till; Bot, Maarten; Green, Alexander L.; Kübler, Dorothee; Lachenmayer, M. Lenard; Debove, Ines; Segura-Amil, Alba; Horn, Andreas; Visser-Vandewalle, Veerle; Schuurman, Rick; Barbe, Michael; Aziz, Tipu Z. (May 2022). "Probabilistic Mapping Reveals Optimal Stimulation Site in Essential Tremor". Annals of Neurology. 91 (5): 602–612. doi:10.1002/ana.26324. ISSN 0364-5134. PMID 35150172. <a href="https://onlinelibrary.wiley.com/doi/10.1002/ana.26324" target="_blank">https://onlinelibrary.wiley.com/doi/10.1002/ana.26324</a> <a href="#fnref:26" class="footnote-back-ref">↩</a></li>
<li id="fn:27">Neudorfer, Clemens; Kroneberg, Daniel; Al-Fatly, Bassam; Goede, Lukas; Kübler, Dorothee; Faust, Katharina; van Rienen, Ursula; Tietze, Anna; Picht, Thomas; Herrington, Todd M.; Middlebrooks, Erik H.; Kühn, Andrea; Schneider, Gerd-Helge; Horn, Andreas (May 2022). "Personalizing Deep Brain Stimulation Using Advanced Imaging Sequences". Annals of Neurology. 91 (5): 613–628. doi:10.1002/ana.26326. ISSN 0364-5134. PMID 35165921. <a href="https://onlinelibrary.wiley.com/doi/10.1002/ana.26326" target="_blank">https://onlinelibrary.wiley.com/doi/10.1002/ana.26326</a> <a href="#fnref:27" class="footnote-back-ref">↩</a></li>
<li id="fn:28">Fox, Michael D.; Deuschl, Günther (May 2022). "Converging on a Neuromodulation Target for Tremor". Annals of Neurology. 91 (5): 581–584. doi:10.1002/ana.26361. ISSN 0364-5134. PMID 35362142. <a href="https://onlinelibrary.wiley.com/doi/10.1002/ana.26361" target="_blank">https://onlinelibrary.wiley.com/doi/10.1002/ana.26361</a> <a href="#fnref:28" class="footnote-back-ref">↩</a></li>
<li id="fn:29">Joutsa, Juho; Lipsman, Nir; Horn, Andreas; Cosgrove, G Rees; Fox, Michael D (2023-08-01). "The return of the lesion for localization and therapy". Brain. 146 (8): 3146–3155. doi:10.1093/brain/awad123. ISSN 0006-8950. PMC 10393408. PMID 37040563. <a href="https://academic.oup.com/brain/article/146/8/3146/7114971" target="_blank">https://academic.oup.com/brain/article/146/8/3146/7114971</a> <a href="#fnref:29" class="footnote-back-ref">↩</a></li>
<li id="fn:30">Kupsch, Andreas; Benecke, Reiner; Müller, Jörg; Trottenberg, Thomas; Schneider, Gerd-Helge; Poewe, Werner; Eisner, Wilhelm; Wolters, Alexander; Müller, Jan-Uwe; Deuschl, Günther; Pinsker, Marcus O.; Skogseid, Inger Marie; Roeste, Geir Ketil; Vollmer-Haase, Juliane; Brentrup, Angela (2006-11-09). "Pallidal Deep-Brain Stimulation in Primary Generalized or Segmental Dystonia". New England Journal of Medicine. 355 (19): 1978–1990. doi:10.1056/NEJMoa063618. ISSN 0028-4793. PMID 17093249. <a href="http://www.nejm.org/doi/abs/10.1056/NEJMoa063618" target="_blank">http://www.nejm.org/doi/abs/10.1056/NEJMoa063618</a> <a href="#fnref:30" class="footnote-back-ref">↩</a></li>
<li id="fn:31">Hollunder, Barbara; Ostrem, Jill L.; Sahin, Ilkem Aysu; Rajamani, Nanditha; Oxenford, Simón; Butenko, Konstantin; Neudorfer, Clemens; Reinhardt, Pablo; Zvarova, Patricia; Polosan, Mircea; Akram, Harith; Vissani, Matteo; Zhang, Chencheng; Sun, Bomin; Navratil, Pavel (March 2024). "Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation". Nature Neuroscience. 27 (3): 573–586. doi:10.1038/s41593-024-01570-1. ISSN 1097-6256. PMC 10917675. PMID 38388734. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917675" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917675</a> <a href="#fnref:31" class="footnote-back-ref">↩</a></li>
<li id="fn:32">Horn, Andreas; Reich, Martin M.; Ewert, Siobhan; Li, Ningfei; Al-Fatly, Bassam; Lange, Florian; Roothans, Jonas; Oxenford, Simon; Horn, Isabel; Paschen, Steffen; Runge, Joachim; Wodarg, Fritz; Witt, Karsten; Nickl, Robert C.; Wittstock, Matthias (2022-04-05). "Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia". Proceedings of the National Academy of Sciences. 119 (14): e2114985119. Bibcode:2022PNAS..11914985H. doi:10.1073/pnas.2114985119. ISSN 0027-8424. PMC 9168456. PMID 35357970. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168456" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168456</a> <a href="#fnref:32" class="footnote-back-ref">↩</a></li>
<li id="fn:33">Butenko, Konstantin; Neudorfer, Clemens; Dembek, Till A.; et al. (2025-01-14). "Engaging dystonia networks with subthalamic stimulation". Proceedings of the National Academy of Sciences. 122 (2): e2417617122. Bibcode:2025PNAS..12217617B. doi:10.1073/pnas.2417617122. ISSN 0027-8424. medRxiv 10.1101/2024.05.24.24307896. PMC 11745339. PMID 39773021. <a href="https://doi.org/10.1073%2Fpnas.2417617122" target="_blank">https://doi.org/10.1073%2Fpnas.2417617122</a> <a href="#fnref:33" class="footnote-back-ref">↩</a></li>
<li id="fn:34">Neumann, Wolf-Julian; Horn, Andreas; Ewert, Siobhan; Huebl, Julius; Brücke, Christof; Slentz, Colleen; Schneider, Gerd-Helge; Kühn, Andrea A. (December 2017). "A localized pallidal physiomarker in cervical dystonia". Annals of Neurology. 82 (6): 912–924. doi:10.1002/ana.25095. ISSN 0364-5134. PMID 29130551. <a href="https://onlinelibrary.wiley.com/doi/10.1002/ana.25095" target="_blank">https://onlinelibrary.wiley.com/doi/10.1002/ana.25095</a> <a href="#fnref:34" class="footnote-back-ref">↩</a></li>
<li id="fn:35">Barow, Ewgenia; Neumann, Wolf-Julian; Brücke, Christof; Huebl, Julius; Horn, Andreas; Brown, Peter; Krauss, Joachim K.; Schneider, Gerd-Helge; Kühn, Andrea A. (November 2014). "Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements". Brain. 137 (11): 3012–3024. doi:10.1093/brain/awu258. ISSN 1460-2156. PMC 4813762. PMID 25212852. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813762" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813762</a> <a href="#fnref:35" class="footnote-back-ref">↩</a></li>
<li id="fn:36">Nuttin, Bart; Cosyns, Paul; Demeulemeester, Hilde; Gybels, Jan; Meyerson, Björn (October 1999). "Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder". The Lancet. 354 (9189): 1526. doi:10.1016/S0140-6736(99)02376-4. PMID 10551504. <a href="https://linkinghub.elsevier.com/retrieve/pii/S0140673699023764" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/S0140673699023764</a> <a href="#fnref:36" class="footnote-back-ref">↩</a></li>
<li id="fn:37">Vandewalle, V; van der Linden, Chr; Groenewegen, Hj; Caemaert, J (February 1999). "Stereotactic treatment of Gilles de la Tourette syndrome by high frequency stimulation of thalamus". The Lancet. 353 (9154): 724. doi:10.1016/S0140-6736(98)05964-9. PMID 10073521. <a href="https://linkinghub.elsevier.com/retrieve/pii/S0140673698059649" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/S0140673698059649</a> <a href="#fnref:37" class="footnote-back-ref">↩</a></li>
<li id="fn:38">Krauss, Joachim K; Pohle, Thomas; Weber, Sabine; Ozdoba, Christoph; Burgunder, Jean-Marc (September 1999). "Bilateral stimulation of globus pallidus internus for treatment of cervical dystonia". The Lancet. 354 (9181): 837–838. doi:10.1016/S0140-6736(99)80022-1. PMID 10485734. <a href="https://linkinghub.elsevier.com/retrieve/pii/S0140673699800221" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/S0140673699800221</a> <a href="#fnref:38" class="footnote-back-ref">↩</a></li>
<li id="fn:39">"FDA Humanitarian Device Exemption Approval for OCD". <a href="https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfhde/hde.cfm?id=375533" target="_blank">https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfhde/hde.cfm?id=375533</a> <a href="#fnref:39" class="footnote-back-ref">↩</a></li>
<li id="fn:40">Visser-Vandewalle, Veerle; Andrade, Pablo; Mosley, Philip E.; Greenberg, Benjamin D.; Schuurman, Rick; McLaughlin, Nicole C.; Voon, Valerie; Krack, Paul; Foote, Kelly D.; Mayberg, Helen S.; Figee, Martijn; Kopell, Brian H.; Polosan, Mircea; Joyce, Eileen M.; Chabardes, Stephan (August 2022). "Deep brain stimulation for obsessive–compulsive disorder: a crisis of access". Nature Medicine. 28 (8): 1529–1532. doi:10.1038/s41591-022-01879-z. ISSN 1078-8956. PMID 35840727. <a href="https://www.nature.com/articles/s41591-022-01879-z" target="_blank">https://www.nature.com/articles/s41591-022-01879-z</a> <a href="#fnref:40" class="footnote-back-ref">↩</a></li>
<li id="fn:41">Mosley, Philip E; Velakoulis, Dennis; Farrand, Sarah; Marsh, Rodney; Mohan, Adith; Castle, David; Sachdev, Perminder S (May 2022). "Deep brain stimulation for treatment-refractory obsessive-compulsive disorder should be an accepted therapy in Australia". Australian & New Zealand Journal of Psychiatry. 56 (5): 430–436. doi:10.1177/00048674211031482. ISSN 0004-8674. PMID 34263654. <a href="http://journals.sagepub.com/doi/10.1177/00048674211031482" target="_blank">http://journals.sagepub.com/doi/10.1177/00048674211031482</a> <a href="#fnref:41" class="footnote-back-ref">↩</a></li>
<li id="fn:42">Sultana B, Panzini MA, Veilleux Carpentier A, Comtois J, Rioux B, Gore G, et al. (April 2021). "Incidence and Prevalence of Drug-Resistant Epilepsy: A Systematic Review and Meta-analysis". Neurology. 96 (17): 805–817. doi:10.1212/WNL.0000000000011839. hdl:1866/26896. PMID 33722992. S2CID 233401199. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:42" class="footnote-back-ref">↩</a></li>
<li id="fn:43">Sperling MR (February 2004). "The consequences of uncontrolled epilepsy". CNS Spectrums. 9 (2): 98–101, 106–9. doi:10.1017/s1092852900008464. PMID 14999166. S2CID 32869839. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:43" class="footnote-back-ref">↩</a></li>
<li id="fn:44">Benbadis, Selim R.; Geller, Eric; Ryvlin, Philippe; Schachter, Steven; Wheless, James; Doyle, Werner; Vale, Fernando L. (November 2018). "Putting it all together: Options for intractable epilepsy". Epilepsy & Behavior. 88: 33–38. doi:10.1016/j.yebeh.2018.05.030. PMID 30241957. <a href="https://linkinghub.elsevier.com/retrieve/pii/S1525505018303834" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/S1525505018303834</a> <a href="#fnref:44" class="footnote-back-ref">↩</a></li>
<li id="fn:45">Vetkas, Artur; Fomenko, Anton; Germann, Jürgen; Sarica, Can; Iorio-Morin, Christian; Samuel, Nardin; Yamamoto, Kazuaki; Milano, Vanessa; Cheyuo, Cletus; Zemmar, Ajmal; Elias, Gavin; Boutet, Alexandre; Loh, Aaron; Santyr, Brendan; Gwun, Dave (March 2022). "Deep brain stimulation targets in epilepsy: Systematic review and meta-analysis of anterior and centromedian thalamic nuclei and hippocampus". Epilepsia. 63 (3): 513–524. doi:10.1111/epi.17157. ISSN 0013-9580. PMID 34981509. <a href="https://onlinelibrary.wiley.com/doi/10.1111/epi.17157" target="_blank">https://onlinelibrary.wiley.com/doi/10.1111/epi.17157</a> <a href="#fnref:45" class="footnote-back-ref">↩</a></li>
<li id="fn:46">Vetkas, Artur; Fomenko, Anton; Germann, Jürgen; Sarica, Can; Iorio-Morin, Christian; Samuel, Nardin; Yamamoto, Kazuaki; Milano, Vanessa; Cheyuo, Cletus; Zemmar, Ajmal; Elias, Gavin; Boutet, Alexandre; Loh, Aaron; Santyr, Brendan; Gwun, Dave (March 2022). "Deep brain stimulation targets in epilepsy: Systematic review and meta-analysis of anterior and centromedian thalamic nuclei and hippocampus". Epilepsia. 63 (3): 513–524. doi:10.1111/epi.17157. ISSN 0013-9580. PMID 34981509. <a href="https://onlinelibrary.wiley.com/doi/10.1111/epi.17157" target="_blank">https://onlinelibrary.wiley.com/doi/10.1111/epi.17157</a> <a href="#fnref:46" class="footnote-back-ref">↩</a></li>
<li id="fn:47">Yan, Hao; Ren, Liankun; Yu, Tao (December 2022). "Deep brain stimulation of the subthalamic nucleus for epilepsy". Acta Neurologica Scandinavica. 146 (6): 798–804. doi:10.1111/ane.13707. ISSN 0001-6314. PMID 36134756. <a href="https://doi.org/10.1111%2Fane.13707" target="_blank">https://doi.org/10.1111%2Fane.13707</a> <a href="#fnref:47" class="footnote-back-ref">↩</a></li>
<li id="fn:48">Vandewalle, V; van der Linden, Chr; Groenewegen, Hj; Caemaert, J (February 1999). "Stereotactic treatment of Gilles de la Tourette syndrome by high frequency stimulation of thalamus". The Lancet. 353 (9154): 724. doi:10.1016/S0140-6736(98)05964-9. PMID 10073521. <a href="https://linkinghub.elsevier.com/retrieve/pii/S0140673698059649" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/S0140673698059649</a> <a href="#fnref:48" class="footnote-back-ref">↩</a></li>
<li id="fn:49">Hassler, Rolf (1970). "raitement stéréotaxique des tics et cris inarticulés ou coprolaliques considérés comme phénomene d'obsession motrice au cours de la maladie de Gilles de la Tourette". Rev Neurol. <a href="#fnref:49" class="footnote-back-ref">↩</a></li>
<li id="fn:50">Singer HS (2011). "Tourette syndrome and other tic disorders". Hyperkinetic Movement Disorders. Handbook of Clinical Neurology. Vol. 100. pp. 641–657. doi:10.1016/B978-0-444-52014-2.00046-X. ISBN 978-0-444-52014-2. PMID 21496613. Also see Singer HS (March 2005). "Tourette's syndrome: from behaviour to biology". The Lancet. Neurology. 4 (3): 149–159. doi:10.1016/S1474-4422(05)01012-4 (inactive 11 January 2025). PMID 15721825. S2CID 20181150.{{cite journal}}: CS1 maint: DOI inactive as of January 2025 (link) <a href="978-0-444-52014-2" target="_blank">978-0-444-52014-2</a> <a href="#fnref:50" class="footnote-back-ref">↩</a></li>
<li id="fn:51">Robertson MM (February 2011). "Gilles de la Tourette syndrome: the complexities of phenotype and treatment". British Journal of Hospital Medicine. 72 (2): 100–107. doi:10.12968/hmed.2011.72.2.100. PMID 21378617. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:51" class="footnote-back-ref">↩</a></li>
<li id="fn:52">Du JC, Chiu TF, Lee KM, Wu HL, Yang YC, Hsu SY, et al. (October 2010). "Tourette syndrome in children: an updated review". Pediatrics and Neonatology. 51 (5): 255–264. doi:10.1016/S1875-9572(10)60050-2. PMID 20951354. <a href="https://doi.org/10.1016%2FS1875-9572%2810%2960050-2" target="_blank">https://doi.org/10.1016%2FS1875-9572%2810%2960050-2</a> <a href="#fnref:52" class="footnote-back-ref">↩</a></li>
<li id="fn:53">Tourette Syndrome Association. Statement: Deep Brain Stimulation and Tourette Syndrome. Retrieved November 22, 2005. <a href="/wiki/Tourette_Association_of_America" target="_blank">/wiki/Tourette_Association_of_America</a> <a href="#fnref:53" class="footnote-back-ref">↩</a></li>
<li id="fn:54">Walkup JT, Mink JW, Hollenbeck PJ (2006). "Behavioral neurosurgery". Tourette Syndrome. Advances in Neurology. Vol. 99. Lippincott Williams & Wilkins. pp. 241–247. ISBN 978-0-7817-9970-6. PMID 16536372. <a href="978-0-7817-9970-6" target="_blank">978-0-7817-9970-6</a> <a href="#fnref:54" class="footnote-back-ref">↩</a></li>
<li id="fn:55">Mink JW, Walkup J, Frey KA, Como P, Cath D, Delong MR, et al. (November 2006). "Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome". Movement Disorders. 21 (11): 1831–1838. doi:10.1002/mds.21039. hdl:2027.42/55891. PMID 16991144. S2CID 16353255. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:55" class="footnote-back-ref">↩</a></li>
<li id="fn:56">Robertson MM (February 2011). "Gilles de la Tourette syndrome: the complexities of phenotype and treatment". British Journal of Hospital Medicine. 72 (2): 100–107. doi:10.12968/hmed.2011.72.2.100. PMID 21378617. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:56" class="footnote-back-ref">↩</a></li>
<li id="fn:57">Walkup JT, Mink JW, Hollenbeck PJ (2006). "Behavioral neurosurgery". Tourette Syndrome. Advances in Neurology. Vol. 99. Lippincott Williams & Wilkins. pp. 241–247. ISBN 978-0-7817-9970-6. PMID 16536372. <a href="978-0-7817-9970-6" target="_blank">978-0-7817-9970-6</a> <a href="#fnref:57" class="footnote-back-ref">↩</a></li>
<li id="fn:58">Du JC, Chiu TF, Lee KM, Wu HL, Yang YC, Hsu SY, et al. (October 2010). "Tourette syndrome in children: an updated review". Pediatrics and Neonatology. 51 (5): 255–264. doi:10.1016/S1875-9572(10)60050-2. PMID 20951354. <a href="https://doi.org/10.1016%2FS1875-9572%2810%2960050-2" target="_blank">https://doi.org/10.1016%2FS1875-9572%2810%2960050-2</a> <a href="#fnref:58" class="footnote-back-ref">↩</a></li>
<li id="fn:59">Singer HS (2011). "Tourette syndrome and other tic disorders". Hyperkinetic Movement Disorders. Handbook of Clinical Neurology. Vol. 100. pp. 641–657. doi:10.1016/B978-0-444-52014-2.00046-X. ISBN 978-0-444-52014-2. PMID 21496613. Also see Singer HS (March 2005). "Tourette's syndrome: from behaviour to biology". The Lancet. Neurology. 4 (3): 149–159. doi:10.1016/S1474-4422(05)01012-4 (inactive 11 January 2025). PMID 15721825. S2CID 20181150.{{cite journal}}: CS1 maint: DOI inactive as of January 2025 (link) <a href="978-0-444-52014-2" target="_blank">978-0-444-52014-2</a> <a href="#fnref:59" class="footnote-back-ref">↩</a></li>
<li id="fn:60">Viswanathan A, Jimenez-Shahed J, Baizabal Carvallo JF, Jankovic J (2012). "Deep brain stimulation for Tourette syndrome: target selection". Stereotactic and Functional Neurosurgery. 90 (4): 213–224. doi:10.1159/000337776. PMID 22699684. <a href="https://doi.org/10.1159%2F000337776" target="_blank">https://doi.org/10.1159%2F000337776</a> <a href="#fnref:60" class="footnote-back-ref">↩</a></li>
<li id="fn:61">Mayberg, Helen S.; Lozano, Andres M.; Voon, Valerie; McNeely, Heather E.; Seminowicz, David; Hamani, Clement; Schwalb, Jason M.; Kennedy, Sidney H. (March 2005). "Deep Brain Stimulation for Treatment-Resistant Depression". Neuron. 45 (5): 651–660. doi:10.1016/j.neuron.2005.02.014. PMID 15748841. <a href="https://linkinghub.elsevier.com/retrieve/pii/S089662730500156X" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/S089662730500156X</a> <a href="#fnref:61" class="footnote-back-ref">↩</a></li>
<li id="fn:62">Dougherty, Darin D.; Rezai, Ali R.; Carpenter, Linda L.; Howland, Robert H.; Bhati, Mahendra T.; O'Reardon, John P.; Eskandar, Emad N.; Baltuch, Gordon H.; Machado, Andre D.; Kondziolka, Douglas; Cusin, Cristina; Evans, Karleyton C.; Price, Lawrence H.; Jacobs, Karen; Pandya, Mayur (August 2015). "A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression". Biological Psychiatry. 78 (4): 240–248. doi:10.1016/j.biopsych.2014.11.023. PMID 25726497. <a href="https://linkinghub.elsevier.com/retrieve/pii/S0006322314009688" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/S0006322314009688</a> <a href="#fnref:62" class="footnote-back-ref">↩</a></li>
<li id="fn:63">Choi, Ki Sueng; Riva-Posse, Patricio; Gross, Robert E.; Mayberg, Helen S. (2015-11-01). "Mapping the "Depression Switch" During Intraoperative Testing of Subcallosal Cingulate Deep Brain Stimulation". JAMA Neurology. 72 (11): 1252–1260. doi:10.1001/jamaneurol.2015.2564. ISSN 2168-6149. PMC 4834289. PMID 26408865. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834289" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834289</a> <a href="#fnref:63" class="footnote-back-ref">↩</a></li>
<li id="fn:64">Riva-Posse, P; Choi, K S; Holtzheimer, P E; Crowell, A L; Garlow, S J; Rajendra, J K; McIntyre, C C; Gross, R E; Mayberg, H S (April 2018). "A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression". Molecular Psychiatry. 23 (4): 843–849. doi:10.1038/mp.2017.59. ISSN 1359-4184. PMC 5636645. PMID 28397839. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636645" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636645</a> <a href="#fnref:64" class="footnote-back-ref">↩</a></li>
<li id="fn:65">Coenen, Volker A.; Schlaepfer, Thomas E.; Varkuti, Balint; Schuurman, P. Rick; Reinacher, Peter C.; Voges, Juergen; Zrinzo, Ludvic; Blomstedt, Patric; Fenoy, Albert J.; Hariz, Marwan (November 2019). "Surgical decision making for deep brain stimulation should not be based on aggregated normative data mining". Brain Stimulation. 12 (6): 1345–1348. doi:10.1016/j.brs.2019.07.014. PMID 31353286. <a href="https://linkinghub.elsevier.com/retrieve/pii/S1935861X19302980" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/S1935861X19302980</a> <a href="#fnref:65" class="footnote-back-ref">↩</a></li>
<li id="fn:66">Coenen, Volker A.; Döbrössy, Máté D.; Teo, Shi Jia; Wessolleck, Johanna; Sajonz, Bastian E. A.; Reinacher, Peter C.; Thierauf-Emberger, Annette; Spittau, Björn; Leupold, Jochen; von Elverfeldt, Dominik; Schlaepfer, Thomas E.; Reisert, Marco (January 2022). "Diverging prefrontal cortex fiber connection routes to the subthalamic nucleus and the mesencephalic ventral tegmentum investigated with long range (normative) and short range (ex-vivo high resolution) 7T DTI". Brain Structure and Function. 227 (1): 23–47. doi:10.1007/s00429-021-02373-x. ISSN 1863-2653. PMC 8741702. PMID 34482443. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741702" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741702</a> <a href="#fnref:66" class="footnote-back-ref">↩</a></li>
<li id="fn:67">Coenen, Volker A.; Honey, Christopher R.; Hurwitz, Trevor; Rahman, Ahmed A.; McMaster, Jacqueline; Bürgel, Uli; Mädler, Burkhard (June 2009). "Medial Forebrain Bundle Stimulation As a Pathophysiological Mechanism for Hypomania in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease". Neurosurgery. 64 (6): 1106–1115. doi:10.1227/01.NEU.0000345631.54446.06. ISSN 0148-396X. PMID 19487890. <a href="https://journals.lww.com/00006123-200906000-00011" target="_blank">https://journals.lww.com/00006123-200906000-00011</a> <a href="#fnref:67" class="footnote-back-ref">↩</a></li>
<li id="fn:68">Volkmann, Jens; Daniels, Christine; Witt, Karsten (September 2010). "Neuropsychiatric effects of subthalamic neurostimulation in Parkinson disease". Nature Reviews Neurology. 6 (9): 487–498. doi:10.1038/nrneurol.2010.111. ISSN 1759-4758. PMID 20680036. <a href="https://www.nature.com/articles/nrneurol.2010.111" target="_blank">https://www.nature.com/articles/nrneurol.2010.111</a> <a href="#fnref:68" class="footnote-back-ref">↩</a></li>
<li id="fn:69">Bouthour, Walid; Mégevand, Pierre; Donoghue, John; Lüscher, Christian; Birbaumer, Niels; Krack, Paul (June 2019). "Biomarkers for closed-loop deep brain stimulation in Parkinson disease and beyond". Nature Reviews Neurology. 15 (6): 343–352. doi:10.1038/s41582-019-0166-4. ISSN 1759-4758. PMID 30936569. <a href="https://www.nature.com/articles/s41582-019-0166-4" target="_blank">https://www.nature.com/articles/s41582-019-0166-4</a> <a href="#fnref:69" class="footnote-back-ref">↩</a></li>
<li id="fn:70">Coenen, Volker A.; Döbrössy, Máté D.; Teo, Shi Jia; Wessolleck, Johanna; Sajonz, Bastian E. A.; Reinacher, Peter C.; Thierauf-Emberger, Annette; Spittau, Björn; Leupold, Jochen; von Elverfeldt, Dominik; Schlaepfer, Thomas E.; Reisert, Marco (January 2022). "Diverging prefrontal cortex fiber connection routes to the subthalamic nucleus and the mesencephalic ventral tegmentum investigated with long range (normative) and short range (ex-vivo high resolution) 7T DTI". Brain Structure and Function. 227 (1): 23–47. doi:10.1007/s00429-021-02373-x. ISSN 1863-2653. PMC 8741702. PMID 34482443. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741702" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741702</a> <a href="#fnref:70" class="footnote-back-ref">↩</a></li>
<li id="fn:71">Haber, Suzanne N.; Yendiki, Anastasia; Jbabdi, Saad (November 2021). "Four Deep Brain Stimulation Targets for Obsessive-Compulsive Disorder: Are They Different?". Biological Psychiatry. 90 (10): 667–677. doi:10.1016/j.biopsych.2020.06.031. PMC 9569132. PMID 32951818. <a href="/wiki/Anastasia_Yendiki" target="_blank">/wiki/Anastasia_Yendiki</a> <a href="#fnref:71" class="footnote-back-ref">↩</a></li>
<li id="fn:72">Bouthour, Walid; Mégevand, Pierre; Donoghue, John; Lüscher, Christian; Birbaumer, Niels; Krack, Paul (June 2019). "Biomarkers for closed-loop deep brain stimulation in Parkinson disease and beyond". Nature Reviews Neurology. 15 (6): 343–352. doi:10.1038/s41582-019-0166-4. ISSN 1759-4758. PMID 30936569. <a href="https://www.nature.com/articles/s41582-019-0166-4" target="_blank">https://www.nature.com/articles/s41582-019-0166-4</a> <a href="#fnref:72" class="footnote-back-ref">↩</a></li>
<li id="fn:73">Bewernick, Bettina H.; Kayser, Sarah; Gippert, Sabrina M.; Switala, Christina; Coenen, Volker A.; Schlaepfer, Thomas E. (May 2017). "Deep brain stimulation to the medial forebrain bundle for depression- long-term outcomes and a novel data analysis strategy". Brain Stimulation. 10 (3): 664–671. doi:10.1016/j.brs.2017.01.581. PMID 28259544. <a href="https://linkinghub.elsevier.com/retrieve/pii/S1935861X17306034" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/S1935861X17306034</a> <a href="#fnref:73" class="footnote-back-ref">↩</a></li>
<li id="fn:74">Young RF, Brechner T (March 1986). "Electrical stimulation of the brain for relief of intractable pain due to cancer". Cancer. 57 (6): 1266–1272. doi:10.1002/1097-0142(19860315)57:6<1266::aid-cncr2820570634>3.0.co;2-q. PMID 3484665. S2CID 41929961. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:74" class="footnote-back-ref">↩</a></li>
<li id="fn:75">Johnson MI, Oxberry SG, Robb K (2008). "Stimulation-induced analgesia". In Sykes N, Bennett MI & Yuan C-S (ed.). Clinical pain management: Cancer pain (2nd ed.). London: Hodder Arnold. pp. 235–250. ISBN 978-0-340-94007-5. <a href="978-0-340-94007-5" target="_blank">978-0-340-94007-5</a> <a href="#fnref:75" class="footnote-back-ref">↩</a></li>
<li id="fn:76">Kringelbach ML, Jenkinson N, Green AL, Owen SL, Hansen PC, Cornelissen PL, et al. (February 2007). "Deep brain stimulation for chronic pain investigated with magnetoencephalography". NeuroReport. 18 (3): 223–228. CiteSeerX 10.1.1.511.2667. doi:10.1097/wnr.0b013e328010dc3d. PMID 17314661. S2CID 7091307. <a href="/wiki/CiteSeerX_(identifier)" target="_blank">/wiki/CiteSeerX_(identifier)</a> <a href="#fnref:76" class="footnote-back-ref">↩</a></li>
<li id="fn:77">Krauss JK (2002). "Deep brain stimulation for dystonia in adults. Overview and developments". Stereotactic and Functional Neurosurgery. 78 (3–4): 168–182. doi:10.1159/000068963. PMID 12652041. S2CID 71888143. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:77" class="footnote-back-ref">↩</a></li>
<li id="fn:78">Wu C, Sharan AD (January–February 2013). "Neurostimulation for the treatment of epilepsy: a review of current surgical interventions". Neuromodulation. 16 (1): 10–24, discussion 24. doi:10.1111/j.1525-1403.2012.00501.x. PMID 22947069. S2CID 1711587. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:78" class="footnote-back-ref">↩</a></li>
<li id="fn:79">Heath RG (January 1972). "Pleasure and brain activity in man. Deep and surface electroencephalograms during orgasm". The Journal of Nervous and Mental Disease. 154 (1): 3–18. doi:10.1097/00005053-197201000-00002. PMID 5007439. S2CID 136706. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:79" class="footnote-back-ref">↩</a></li>
<li id="fn:80">Faria MA (2013). "Violence, mental illness, and the brain - A brief history of psychosurgery: Part 3 - From deep brain stimulation to amygdalotomy for violent behavior, seizures, and pathological aggression in humans". Surgical Neurology International. 4 (1): 91. doi:10.4103/2152-7806.115162. PMC 3740620. PMID 23956934. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740620" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740620</a> <a href="#fnref:80" class="footnote-back-ref">↩</a></li>
<li id="fn:81">Surbeck W, Bouthillier A, Nguyen DK (2013). "Bilateral cortical representation of orgasmic ecstasy localized by depth electrodes". Epilepsy & Behavior Case Reports. 1: 62–65. doi:10.1016/j.ebcr.2013.03.002. PMC 4150648. PMID 25667829. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150648" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150648</a> <a href="#fnref:81" class="footnote-back-ref">↩</a></li>
<li id="fn:82">Fonoff ET, Azevedo A, Angelos JS, Martinez RC, Navarro J, Reis PR, et al. (July 2016). "Simultaneous bilateral stereotactic procedure for deep brain stimulation implants: a significant step for reducing operation time". Journal of Neurosurgery. 125 (1): 85–89. doi:10.3171/2015.7.JNS151026. PMID 26684776. <a href="https://doi.org/10.3171%2F2015.7.JNS151026" target="_blank">https://doi.org/10.3171%2F2015.7.JNS151026</a> <a href="#fnref:82" class="footnote-back-ref">↩</a></li>
<li id="fn:83">Lu H, Ash RT, He L, Kee SE, Wang W, Yu D, et al. (August 2016). "Loss and Gain of MeCP2 Cause Similar Hippocampal Circuit Dysfunction that Is Rescued by Deep Brain Stimulation in a Rett Syndrome Mouse Model". Neuron. 91 (4): 739–747. doi:10.1016/j.neuron.2016.07.018. PMC 5019177. PMID 27499081. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019177" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019177</a> <a href="#fnref:83" class="footnote-back-ref">↩</a></li>
<li id="fn:84">Pohodich AE, Yalamanchili H, Raman AT, Wan YW, Gundry M, Hao S, et al. (March 2018). "Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and plasticity". eLife. 7. doi:10.7554/elife.34031. PMC 5906096. PMID 29570050. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906096" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906096</a> <a href="#fnref:84" class="footnote-back-ref">↩</a></li>
<li id="fn:85">Visser-Vandewalle, Veerle; Andrade, Pablo; Mosley, Philip E.; Greenberg, Benjamin D.; Schuurman, Rick; McLaughlin, Nicole C.; Voon, Valerie; Krack, Paul; Foote, Kelly D.; Mayberg, Helen S.; Figee, Martijn; Kopell, Brian H.; Polosan, Mircea; Joyce, Eileen M.; Chabardes, Stephan (August 2022). "Deep brain stimulation for obsessive–compulsive disorder: a crisis of access". Nature Medicine. 28 (8): 1529–1532. doi:10.1038/s41591-022-01879-z. ISSN 1078-8956. PMID 35840727. <a href="https://www.nature.com/articles/s41591-022-01879-z" target="_blank">https://www.nature.com/articles/s41591-022-01879-z</a> <a href="#fnref:85" class="footnote-back-ref">↩</a></li>
<li id="fn:86">Benabid, A.L.; Pollak, P.; Hoffmann, D.; Gervason, C.; Hommel, M.; Perret, J.E.; de Rougemont, J.; Gao, D.M. (February 1991). "Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus". The Lancet. 337 (8738): 403–406. doi:10.1016/0140-6736(91)91175-T. PMID 1671433. <a href="https://linkinghub.elsevier.com/retrieve/pii/014067369191175T" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/014067369191175T</a> <a href="#fnref:86" class="footnote-back-ref">↩</a></li>
<li id="fn:87">Deep-Brain Stimulation for Parkinson's Disease Study Group; Obeso, J. A.; Olanow, C. W.; Rodriguez-Oroz, M. C.; Krack, P.; Kumar, R.; Lang, A. E. (2001-09-27). "Deep-Brain Stimulation of the Subthalamic Nucleus or the Pars Interna of the Globus Pallidus in Parkinson's Disease". New England Journal of Medicine. 345 (13): 956–963. doi:10.1056/NEJMoa000827. ISSN 0028-4793. PMID 11575287. <a href="http://www.nejm.org/doi/abs/10.1056/NEJMoa000827" target="_blank">http://www.nejm.org/doi/abs/10.1056/NEJMoa000827</a> <a href="#fnref:87" class="footnote-back-ref">↩</a></li>
<li id="fn:88">Deuschl, Günther; Schade-Brittinger, Carmen; Krack, Paul; Volkmann, Jens; Schäfer, Helmut; Bötzel, Kai; Daniels, Christine; Deutschländer, Angela; Dillmann, Ulrich; Eisner, Wilhelm; Gruber, Doreen; Hamel, Wolfgang; Herzog, Jan; Hilker, Rüdiger; Klebe, Stephan (2006-08-31). "A Randomized Trial of Deep-Brain Stimulation for Parkinson's Disease". New England Journal of Medicine. 355 (9): 896–908. doi:10.1056/NEJMoa060281. ISSN 0028-4793. PMID 16943402. <a href="http://www.nejm.org/doi/abs/10.1056/NEJMoa060281" target="_blank">http://www.nejm.org/doi/abs/10.1056/NEJMoa060281</a> <a href="#fnref:88" class="footnote-back-ref">↩</a></li>
<li id="fn:89">Vidailhet, Marie; Vercueil, Laurent; Houeto, Jean-Luc; Krystkowiak, Pierre; Benabid, Alim-Louis; Cornu, Philippe; Lagrange, Christelle; Tézenas du Montcel, Sophie; Dormont, Didier; Grand, Sylvie; Blond, Serge; Detante, Olivier; Pillon, Bernard; Ardouin, Claire; Agid, Yves (2005-02-03). "Bilateral Deep-Brain Stimulation of the Globus Pallidus in Primary Generalized Dystonia". New England Journal of Medicine. 352 (5): 459–467. doi:10.1056/NEJMoa042187. ISSN 0028-4793. PMID 15689584. <a href="http://www.nejm.org/doi/10.1056/NEJMoa042187" target="_blank">http://www.nejm.org/doi/10.1056/NEJMoa042187</a> <a href="#fnref:89" class="footnote-back-ref">↩</a></li>
<li id="fn:90">Kupsch, Andreas; Benecke, Reiner; Müller, Jörg; Trottenberg, Thomas; Schneider, Gerd-Helge; Poewe, Werner; Eisner, Wilhelm; Wolters, Alexander; Müller, Jan-Uwe; Deuschl, Günther; Pinsker, Marcus O.; Skogseid, Inger Marie; Roeste, Geir Ketil; Vollmer-Haase, Juliane; Brentrup, Angela (2006-11-09). "Pallidal Deep-Brain Stimulation in Primary Generalized or Segmental Dystonia". New England Journal of Medicine. 355 (19): 1978–1990. doi:10.1056/NEJMoa063618. ISSN 0028-4793. PMID 17093249. <a href="http://www.nejm.org/doi/abs/10.1056/NEJMoa063618" target="_blank">http://www.nejm.org/doi/abs/10.1056/NEJMoa063618</a> <a href="#fnref:90" class="footnote-back-ref">↩</a></li>
<li id="fn:91">Nuttin, Bart J.; Gabriëls, Loes A.; Cosyns, Paul R.; Meyerson, Björn A.; Andréewitch, Sergej; Sunaert, Stefan G.; Maes, Alex F.; Dupont, Patrick J.; Gybels, Jan M.; Gielen, Frans; Demeulemeester, Hilde G. (June 2003). "Long-term Electrical Capsular Stimulation in Patients with Obsessive-Compulsive Disorder". Neurosurgery. 52 (6): 1263–1274. doi:10.1227/01.NEU.0000064565.49299.9A. ISSN 0148-396X. PMID 12762871. <a href="https://journals.lww.com/00006123-200306000-00002" target="_blank">https://journals.lww.com/00006123-200306000-00002</a> <a href="#fnref:91" class="footnote-back-ref">↩</a></li>
<li id="fn:92">Fisher, Robert; Salanova, Vicenta; Witt, Thomas; Worth, Robert; Henry, Thomas; Gross, Robert; Oommen, Kalarickal; Osorio, Ivan; Nazzaro, Jules; Labar, Douglas; Kaplitt, Michael; Sperling, Michael; Sandok, Evan; Neal, John; Handforth, Adrian (May 2010). "Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy". Epilepsia. 51 (5): 899–908. doi:10.1111/j.1528-1167.2010.02536.x. ISSN 0013-9580. PMID 20331461. <a href="https://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2010.02536.x" target="_blank">https://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2010.02536.x</a> <a href="#fnref:92" class="footnote-back-ref">↩</a></li>
<li id="fn:93">"FDA approves brain implant to help reduce Parkinson's disease and essential tremor symptoms". FDA. Retrieved May 23, 2016. The first device, Medtronic's Activa Deep Brain Stimulation Therapy System, was approved in 1997 for tremor associated with essential tremor and Parkinson's disease. <a href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm451152.htm" target="_blank">https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm451152.htm</a> <a href="#fnref:93" class="footnote-back-ref">↩</a></li>
<li id="fn:94">Phillips S (17 June 2007). "'Brain pacemaker' for a rare disorder". NBC News. Archived from the original on April 28, 2021. <a href="https://web.archive.org/web/20210428014405/https://www.nbcnews.com/id/wbna19265007" target="_blank">https://web.archive.org/web/20210428014405/https://www.nbcnews.com/id/wbna19265007</a> <a href="#fnref:94" class="footnote-back-ref">↩</a></li>
<li id="fn:95">"Medtronic Receives FDA Approval for Deep Brain Stimulation Therapy for Medically Refractory Epilepsy" (Press release). Medtronic. 1 May 2018. <a href="https://news.medtronic.com/2018-05-01-Medtronic-Receives-FDA-Approval-for-Deep-Brain-Stimulation-Therapy-for-Medically-Refractory-Epilepsy" target="_blank">https://news.medtronic.com/2018-05-01-Medtronic-Receives-FDA-Approval-for-Deep-Brain-Stimulation-Therapy-for-Medically-Refractory-Epilepsy</a> <a href="#fnref:95" class="footnote-back-ref">↩</a></li>
<li id="fn:96">"FDA Approves Humanitarian Device Exemption for Deep Brain Stimulator for Severe Obsessive-Compulsive Disorder". FDA. <a href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149529.htm" target="_blank">https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149529.htm</a> <a href="#fnref:96" class="footnote-back-ref">↩</a></li>
<li id="fn:97">Morris JG, Owler B, Hely MA, Fung VS (2007). "Hydrocephalus and structural lesions". Parkinson's Disease and Related Disorders, Part II. Handbook of Clinical Neurology. Vol. 84. pp. 459–478. doi:10.1016/S0072-9752(07)84055-3. ISBN 978-0-444-52893-3. OCLC 1132129865. PMID 18808964. <a href="978-0-444-52893-3" target="_blank">978-0-444-52893-3</a> <a href="#fnref:97" class="footnote-back-ref">↩</a></li>
<li id="fn:98">Grill, Warren M.; Snyder, Andrea N.; Miocinovic, Svjetlana (May 2004). "Deep brain stimulation creates an informational lesion of the stimulated nucleus". NeuroReport. 15 (7): 1137–1140. doi:10.1097/00001756-200405190-00011. ISSN 0959-4965. PMID 15129161. <a href="http://journals.lww.com/00001756-200405190-00011" target="_blank">http://journals.lww.com/00001756-200405190-00011</a> <a href="#fnref:98" class="footnote-back-ref">↩</a></li>
<li id="fn:99">Hollunder, Barbara; Ostrem, Jill L.; Sahin, Ilkem Aysu; Rajamani, Nanditha; Oxenford, Simón; Butenko, Konstantin; Neudorfer, Clemens; Reinhardt, Pablo; Zvarova, Patricia; Polosan, Mircea; Akram, Harith; Vissani, Matteo; Zhang, Chencheng; Sun, Bomin; Navratil, Pavel (March 2024). "Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation". Nature Neuroscience. 27 (3): 573–586. doi:10.1038/s41593-024-01570-1. ISSN 1097-6256. PMC 10917675. PMID 38388734. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917675" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917675</a> <a href="#fnref:99" class="footnote-back-ref">↩</a></li>
<li id="fn:100">Follett, Kenneth A.; Weaver, Frances M.; Stern, Matthew; Hur, Kwan; Harris, Crystal L.; Luo, Ping; Marks, William J.; Rothlind, Johannes; Sagher, Oren; Moy, Claudia; Pahwa, Rajesh; Burchiel, Kim; Hogarth, Penelope; Lai, Eugene C.; Duda, John E. (2010-06-03). "Pallidal versus Subthalamic Deep-Brain Stimulation for Parkinson's Disease". New England Journal of Medicine. 362 (22): 2077–2091. doi:10.1056/NEJMoa0907083. ISSN 0028-4793. PMID 20519680. <a href="http://www.nejm.org/doi/abs/10.1056/NEJMoa0907083" target="_blank">http://www.nejm.org/doi/abs/10.1056/NEJMoa0907083</a> <a href="#fnref:100" class="footnote-back-ref">↩</a></li>
<li id="fn:101">Doshi PK (April 2011). "Long-term surgical and hardware-related complications of deep brain stimulation". Stereotactic and Functional Neurosurgery. 89 (2): 89–95. doi:10.1159/000323372. PMID 21293168. S2CID 10553177. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:101" class="footnote-back-ref">↩</a></li>
<li id="fn:102">Scangos KW, Makhoul GS, Sugrue LP, Chang EF, Krystal AD (February 2021). "State-dependent responses to intracranial brain stimulation in a patient with depression". Nature Medicine. 27 (2): 229–231. doi:10.1038/s41591-020-01175-8. PMC 8284979. PMID 33462446. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284979" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284979</a> <a href="#fnref:102" class="footnote-back-ref">↩</a></li>
<li id="fn:103">Burn DJ, Tröster AI (September 2004). "Neuropsychiatric complications of medical and surgical therapies for Parkinson's disease". Journal of Geriatric Psychiatry and Neurology. 17 (3): 172–180. doi:10.1177/0891988704267466. PMID 15312281. S2CID 441486. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:103" class="footnote-back-ref">↩</a></li>
<li id="fn:104">George J (27 November 2019). "Deep Brain Stimulation May Put Parkinson's Patients at Risk for Drowning". MedPage Today. <a href="https://www.medpagetoday.com/geriatrics/parkinsonsdisease/83610" target="_blank">https://www.medpagetoday.com/geriatrics/parkinsonsdisease/83610</a> <a href="#fnref:104" class="footnote-back-ref">↩</a></li>
<li id="fn:105">Bangash OK, Thorburn M, Garcia-Vega J, Walters S, Stell R, Starkstein SE, Lind CR (May 2016). "Drowning hazard with deep brain stimulation: case report". Journal of Neurosurgery. 124 (5): 1513–1516. doi:10.3171/2015.5.JNS15589. PMID 26566200. <a href="https://doi.org/10.3171%2F2015.5.JNS15589" target="_blank">https://doi.org/10.3171%2F2015.5.JNS15589</a> <a href="#fnref:105" class="footnote-back-ref">↩</a></li>
<li id="fn:106">Mogilner A.Y.; Benabid A.L.; Rezai A.R. (2004). "Chronic Therapeutic Brain Stimulation: History, Current Clinical Indications, and Future Prospects". In Markov, Marko; Paul J. Rosch (eds.). Bioelectromagnetic medicine. New York: Marcel Dekker. pp. 133–151. ISBN 978-0-8247-4700-8. <a href="978-0-8247-4700-8" target="_blank">978-0-8247-4700-8</a> <a href="#fnref:106" class="footnote-back-ref">↩</a></li>
<li id="fn:107">McIntyre CC, Thakor NV (2002). "Uncovering the mechanisms of deep brain stimulation for Parkinson's disease through functional imaging, neural recording, and neural modeling". Critical Reviews in Biomedical Engineering. 30 (4–6): 249–281. doi:10.1615/critrevbiomedeng.v30.i456.20. PMID 12739751. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:107" class="footnote-back-ref">↩</a></li>
<li id="fn:108">Herrington TM, Cheng JJ, Eskandar EN (January 2016). "Mechanisms of deep brain stimulation". Journal of Neurophysiology. 115 (1): 19–38. doi:10.1152/jn.00281.2015. PMC 4760496. PMID 26510756. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760496" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760496</a> <a href="#fnref:108" class="footnote-back-ref">↩</a></li>
<li id="fn:109">García MR, Pearlmutter BA, Wellstead PE, Middleton RH (16 September 2013). "A slow axon antidromic blockade hypothesis for tremor reduction via deep brain stimulation". PLOS ONE. 8 (9): e73456. Bibcode:2013PLoSO...873456G. doi:10.1371/journal.pone.0073456. PMC 3774723. PMID 24066049. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774723" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774723</a> <a href="#fnref:109" class="footnote-back-ref">↩</a></li>
<li id="fn:110">Machado A, Rezai AR, Kopell BH, Gross RE, Sharan AD, Benabid AL (June 2006). "Deep brain stimulation for Parkinson's disease: surgical technique and perioperative management". Movement Disorders. 21 (Suppl 14): S247 – S258. doi:10.1002/mds.20959. PMID 16810722. S2CID 18194178. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:110" class="footnote-back-ref">↩</a></li>
<li id="fn:111">Moro E, Lang AE (November 2006). "Criteria for deep-brain stimulation in Parkinson's disease: review and analysis". Expert Review of Neurotherapeutics. 6 (11): 1695–1705. doi:10.1586/14737175.6.11.1695. PMID 17144783. S2CID 20857769. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:111" class="footnote-back-ref">↩</a></li>
<li id="fn:112">Apetauerova D, Ryan RK, Ro SI, Arle J, Shils J, Papavassiliou E, Tarsy D (August 2006). "End of day dyskinesia in advanced Parkinson's disease can be eliminated by bilateral subthalamic nucleus or globus pallidus deep brain stimulation". Movement Disorders. 21 (8): 1277–1279. doi:10.1002/mds.20896. PMID 16637040. S2CID 42122286. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:112" class="footnote-back-ref">↩</a></li>
</ol>

Deep brain stimulation open-in-new

Deep brain stimulation