We want to express our gratitude to all the surgical team at La Fe Hospital Valencia for their support and details provided.

This clinical procedure was approved by the Ethical Committee for Biomedical Research of La Fe Hospital with registration number 2015/0824 in May 17, 2016. All participants signed written informed consents. These investigations using human data were carried out following the rules of the Declaration of Helsinki and its updates.
1. Presurgery: Patient screening for DBS implantation
<ol>
	<li>Detect patients with increased drug dosages required to block PD disorders. 
	NOTE: The main drug...

<ol>
	<li>Schapira, A. H., Jenner, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Etiology+and+pathogenesis+of+Parkinson's+disease.">Etiology and pathogenesis of Parkinson's disease.</a> Journal of Movement Disorders. 26 (6), 1049-1055 (2011).</li><li>Dorsey, E. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Projected+number+of+people+with+Parkinson+disease+in+the+most+populous+nations,+2005+through+2030.">Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030.</a> Journal of Neurology. 68 (5), 384-386 (2007).</li><li>Pe&#241;as Domingo, E., Galvez-Sierra, M., Mar&#237;n-Valero, M., Perez-Olivares, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> El libro blanco del Parkinson en Espa&#241;a. , (2015).</li><li>Chaovalitwongse, W., Jeong, Y., Jeong, M. K., Danish, S., Wong, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pattern+Recognition+Approaches+for+Identifying+Subcortical+Targets+during+Deep+Brain+Stimulation+Surgery.">Pattern Recognition Approaches for Identifying Subcortical Targets during Deep Brain Stimulation Surgery.</a> IEEE Intelligent Systems. 26 (5), 54-63 (2011).</li><li>Mavridis, I., Boviatsis, E., Anagnostopoulou, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anatomy+of+the+Human+Subthalamic+Nucleus:+A+Combined+Morphometric+Study.">Anatomy of the Human Subthalamic Nucleus: A Combined Morphometric Study.</a> Anatomy Research International. 2013, 319710 (2013).</li><li>Tepper, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selection+of+the+Optimal+Algorithm+for+Real-Time+Estimation+of+Beta+Band+Power+during+DBS+Surgeries+in+Patients+with+Parkinson's+Disease.">Selection of the Optimal Algorithm for Real-Time Estimation of Beta Band Power during DBS Surgeries in Patients with Parkinson's Disease.</a> Computational Intelligence and Neuroscience. 2017, 1512504 (2017).</li><li>Zaidel, A., Spivak, A., Grieb, B., Bergman, H., Israel, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subthalamic+span+of+&#946;+oscillations+predicts+deep+brain+stimulation+efficacy+for+patients+with+Parkinson's+disease.">Subthalamic span of &#946; oscillations predicts deep brain stimulation efficacy for patients with Parkinson's disease.</a> Brain. 133 (7), 2007-2021 (2010).</li><li>Engel, A. K., Fries, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Beta-band+oscillations-signalling+the+status+quo.">Beta-band oscillations-signalling the status quo.</a> Current Opinion in Neurobiology. 20 (2), 156-165 (2010).</li><li>Wong, S., Baltuch, G. H., Jaggi, J. L., Danish, S. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+localization+and+visualization+of+the+subthalamic+nucleus+from+microelectrode+recordings+acquired+during+DBS+surgery+with+unsupervised+machine+learning.">Functional localization and visualization of the subthalamic nucleus from microelectrode recordings acquired during DBS surgery with unsupervised machine learning.</a> Journal of Neural Engineering. 6 (2), 26006 (2009).</li><li>Abosch, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+International+Survey+of+Deep+Brain+Stimulation+Procedural+Steps.">An International Survey of Deep Brain Stimulation Procedural Steps.</a> Stereotactic and Functional Neurosurgery. 91, 1-11 (2013).</li><li>Shukla, A. W., Okun, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=State+of+the+Art+for+Deep+Brain+Stimulation+Therapy+in+Movement+Disorders:+A+Clinical+and+Technological+Perspective.">State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective.</a> IEEE Reviews in Biomedical Engineering. 9, 219-233 (2016).</li><li>Lang, A. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+brain+stimulation:+Preoperative+issues.">Deep brain stimulation: Preoperative issues.</a> Movement Disorder. 21, 171-196 (2006).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> StealthStation&#174; S7&#174; Treatment Guidance System Manual. , (2012).</li><li>Mashour, G. A., Engelhard, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Oxford Textbook of Neuroscience and Anaesthesiology. , (2019).</li><li>Guerrero, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> DBScan. , (2016).</li></ol>

The main improvements provided by this DBS surgery method are the following: full sedation of the patient, use of a stereotactic robot for electrode insertion, and use of DBScan software for high precision fixation of the stimulation electrodes. The method provides complete confidence about the fixation location, supported by the postsurgical results showing successful blocking of PD effects.
Currently, 5% of the patients required a new DBS surgery. This was due to problems during surgery not ...

Parkinson&#8217;s disease (PD) is a major health problem affecting ~1&#8211;2% of people over 65 years of age worldwide1, causing motor disorders (e.g., bradykinesia, tremor at rest, rigidity, postural instability), and non-motor disorders (e.g., sleep disorders, cognitive dysfunctions)2,3. The deep brain stimulation (DBS) technique consists of applying electrical stimuli to the subthalamic nucleus (STN) region of the brain. This treatment has proved to be very efficient in blocking PD motor disorders in the patient4, allowing a better quality of life.
In order to stimulate the STN, a surgical procedure is necessary to insert one electrode in its left and one in its right region and then fix them in place. The success of the operation, measured by the improvement in the patient&#8217;s quality of life after surgery, greatly depends on the optimal fixation position of the stimulating electrodes. The STN is a relatively small oval region between 4 mm and 10 mm length5, so it is difficult to target. However, it is not only necessary to place the electrodes in the STN but also carefully select the electrode positions within it.
The optimal electrode position is given by the beta band activity. It is widely accepted that the main indicator for PD is directly related to beta band activity measured by the spectral power in the band: higher activity indicates more severe PD disorders6,7. Brain spectral analysis divides the brain waves into bandwidths; the beta spectral band is the frequency band ranging from 13 Hz to 30 Hz. Activity in the beta band is associated with sensorimotor processing, has been observed in various different cortical areas, and is implicated in a wide range of cognitive functions8. When this activity appears in the STN, it is considered to be pathological and associated to PD. Electrical stimulation provided by DBS reduces beta band activity.
The surgical procedure for DBS implantation varies upon the technological equipment available at the hospital and to the neurosurgery team in charge. First, preoperative MRI images are fused with a stereotactic volumetric frame-based CT on the day of surgery for direct anatomical targeting. Then, during surgery, with the use of a stereotactic frame and an arc-shaped device attached to it, it is possible to plot the coordinates and drive the electrode to the exact location and depth in the brain using a mechanically or electrically assisted submillimeter displacement electrode driver. Prior to the placement of the stimulation electrodes, the intraoperative physiological verification of the STN is necessary. For this, a cannula with microelectrodes for signal recording (MER) are inserted at a distance calculated according to the MRI and within planned trajectory and, with the patient awake, some motor activities are performed while the brain signal activity is monitored in order to fine tune the position in view of the brain activity. According to the surgeon and the commonly accepted brain pattern criteria4, the final fixation position is decided. The MER are then extracted, and the stimulation electrodes are inserted and fixed to the specified position. One of the main features of the proposed protocol is that, unlike other methods, the patient is completely sedated and less anxious or uncomfortable. Additionally, the aim of DBS is to reduce the beta band activity in the STN, which will reduce beta activity in the cortex and eliminate the PD disorders. In this case, the fixation position decision for the stimulation electrode is based on the beta band activity in the STN, supported by intraoperative computed tomography (CT) images. The procedure is integrated in a developed software called DBScan that makes use of signal analysis and artificial intelligence algorithms. Some STN localization algorithms are proposed9, but they are not integrated in the surgical procedure and, in practice, they cannot be used. This work describes the use of the DBScan tool for STN localization used during the surgical procedure.
The objective of this work is to describe the method followed during DBS implantation surgery and the novel techniques supporting the operation. The procedure is derived from the standard practices in DBS surgery10,11, but several improvements have been made and results show that all patients obtained satisfactory results (1% had some surgery problems not directly associated to the DBS). In comparison, when using previous surgery methods, 5% of patients required repositioning or had undesired disorder blocking.

<table>
	<tbody>
		<tr>
			<td>CT - Computed Tomography</td>
			<td>Philips</td>
			<td>Brillance Essencial</td>
			<td>Preoperative CT</td>
		</tr>
		<tr>
			<td>DBS lead anchoring</td>
			<td>Medtronic</td>
			<td>Stimloc</td>
			<td>Fixation system for stimulation electrode leads in the skull</td>
		</tr>
		<tr>
			<td>DBS stimulation electrodes</td>
			<td>Medtronic</td>
			<td>model 3389</td>
			<td>4 contacts</td>
		</tr>
		<tr>
			<td>DBScan software</td>
			<td>Univ. Valencia</td>
			<td></td>
			<td>Developed by authors for brain signal analysis and classification</td>
		</tr>
		<tr>
			<td>Frameless patient registration module</td>
			<td>Renishaw</td>
			<td>Neurolocate</td>
			<td>Used for fiducial points</td>
		</tr>
		<tr>
			<td>Image Fusion and trajectory planning software</td>
			<td>Alpha Omega</td>
			<td>Stealthstation S7 with Framelink planning</td>
			<td>Used for target and trajectory definition</td>
		</tr>
		<tr>
			<td>Intraoperative CT</td>
			<td>Medtronic</td>
			<td>O-ARM</td>
			<td>Used for image fusion during DBS surgery</td>
		</tr>
		<tr>
			<td>MER electrodes</td>
			<td>Alpha-Omega</td>
			<td>Acute Electrode</td>
			<td>Tungsten, glass coating, 125mm shank diameter, 2mm exposed wire, 1mm male pin, 1MW</td>
		</tr>
		<tr>
			<td>Miroelectrode and Local Field Potential Register with automatic neuro navigation</td>
			<td>Alpha Omega</td>
			<td>NeuroSmart</td>
			<td>Brain signal recorder and visualizer</td>
		</tr>
		<tr>
			<td>Motorized electrode driver</td>
			<td>Alpha Omega</td>
			<td>Micromotor NeuroNav Drive</td>
			<td>Insertion and extraction of MER and stimulation electrodes</td>
		</tr>
		<tr>
			<td>MRI &#8211; magnetic resonance</td>
			<td>Philips</td>
			<td>Intera 1.5 T</td>
			<td>Preoperative MRI</td>
		</tr>
		<tr>
			<td>S7 Cranial software</td>
			<td>Medtronic</td>
			<td>S7 Cranial software</td>
			<td></td>
		</tr>
		<tr>
			<td>StealthStation S7</td>
			<td>Medtronic</td>
			<td>StealthStation S7</td>
			<td></td>
		</tr>
		<tr>
			<td>Stereotactic frame</td>
			<td>Elekta</td>
			<td>Leksell</td>
			<td>Only used for head support, no skin incisions for fiducial positioning</td>
		</tr>
		<tr>
			<td>Stereotactic robot</td>
			<td>Renishaw</td>
			<td>Neuro Mate</td>
			<td>Substitute of arc-shaped stereotactic frame. Also used for electrode driver support</td>
		</tr>
	</tbody>
</table>

optimal fixation position of deep brain stimulation electrodes for parkinson's disease in humans

Certain cases of Parkinson&#8217;s disease are treated with deep brain stimulation (DBS), applying electrical stimuli to the subthalamic nucleus (STN) in the brain. Stimuli are provided by inserted stimulation electrodes within the brain that supply a square voltage signal generated in a control unit (IPG) typically located in the chest. The elimination of Parkinson&#8217;s symptoms depends directly on the location of the stimulation electrodes. This work describes a method used to determine the best fixation position of the stimulation electrodes during surgery. The procedure provides guidance to the surgeon and requires the use of three techniques: 1) use of a stereotactic frame and stereotactic robot, 2) medical imaging (e.g., MRI and CT), and 3) signal analysis provided by microelectrode recording. In DBS surgery, the patient is usually awake with light sedation; however, one of the main advantages of this method is that the patient is fully sedated with anesthesia to avoid any distress or nervousness. Deciding where to perform electrode fixation is a result of combining intraoperative imaging and signal analysis to detect the the electrode position with the highest probability of blocking the PD symptoms. A software tool for signal analysis (DBScan) was developed, assisting the surgical team in determining the location for electrode fixation. In long-term postsurgical analysis, PD disorders were successfully eliminated in all operated patients.

DBS surgery is the last resort for PD patients who do not respond to drug therapy or patients having adverse side effects with drug therapy (e.g., psychiatric or behavioral disorders). After DBS implantation, the drug dose administered to the patient is reduced by two thirds of the dose before implantation. Additionally, DBS provides better quality of life, reducing tremors and psychological side effects of drugs, and also reduces the number of patient visits to the doctor.
Regarding precision...

The fixation of deep brain stimulation microelectrodes for Parkinson&#8217;s disease requires brain surgery. This work describes a method to determine the optimal position of the stimulation electrodes during surgery, which requires a combination of techniques.

Optimal Fixation Position of Deep Brain Stimulation Electrodes for Parkinson's Disease in Humans

Certain cases of Parkinson&#8217;s disease are treated with deep brain stimulation (DBS), applying electrical stimuli to the subthalamic nucleus (STN) in ...

Optimal Fixation Position of Deep Brain Stimulation Electrodes for Parkinson's Disease in Humans

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