Dr. Antoniades was supported by the National Institute of Health Research (NIHR) and by the Dementias and Neurodegenerative Diseases Research Network (DENDRON) and by the Wellcome Trust. Dr FitzGerald was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre.

yerel etik kurul bu çalışmayı onayladı ve 1. bölümde aşağıda ayrıntılı olarak katılımcıların elde edildi razı bilgilendirir. 1. Katılımcı Onay <ol><li> test oturumu içerecektir ayrıntılı olarak açıklayan bir bilgi notunda katılımcılara sunmak. </li><li> Katılımcılar onay formunda her noktayı açıklayan ve onlara herhangi bir soru sormak için fırsat veren, onlarla onay formu geçmesi, okuma ve çalışma onların alarak kısmına ilişkin herhangi bir sorunuz, endişeniz veya diğer konuları görüşmek için fırsat var sonra onlar olabilir. formu doldurmaları katılımcıdan. </li></ol> 2. Saccadometer kurma <ol><li> Hastanın kafasına cihazı, ayarlanabilir elastik kayış ile güvenli ve burun köprüsü üzerinde dinlenme yerleştirin. uyaranlara kafa ile tam hareket Çünkü, hiçbir kafa kısıtlama gereklidir ve aygıt wea rahattırr. </li><li> Düz mat ekran 1,5 m oturmak için hasta isteyin. </li><li> uyaranlara (kırmızı ışık lekeler) açıkça görülmektedir ki ortam aydınlatması loş olduğundan emin olun. </li></ol> 3. Sakkadik Oturumu kaydetme Not: Prosaccades ve Antisaccades 8 hem test standart bir protokol burada açıklanan Örnek olarak. 60 Prosaccades, 40 Antisaccades x 3 ve bloklar arasındaki 1 dakikalık bir mola ile 60 Prosaccades: Bu protokol, beş bloktan oluşmaktadır. oturumu yaklaşık 40 dakika sürer. <ol><li> O sönmüş ve periferik hedeflerinden biri rastgele sağa ya da sola 9, görünür sonra 2.0 saniye, - her deneme için merkezi fiksasyon hedef 1.0 rastgele ön-dönem için görüntülenecek şekilde saccadometer ayarlayın. Not: Üç hedefleri saccadometer yerleşik düşük güç lazerler ile katılımcının önünde ekrana yansıtılan kırmızı ışık lekeler (2.2 bakınız). saccadometer automatically ekrana ve kapalı lazerleri anahtarları / gerekli sırayla hedefleri söndürmek. </li><li> test blokları arasında bir dakika ara ile beş bloktan oluşuyor katılımcı bilgilendirin. </li><li> Önce ilk blok bir tarafı ya da diğer orta atlayarak kırmızı nokta takip etmek ve bu 60 kez yapmak talimat mümkün olduğunca hızlı ve doğru bir gözlerini taşımak için katılımcı talimat. </li><li> 60 çalışmaların bir dizi oluşturmak için saccadometer ayarlayın. denemeler (Prosaccades) ilk bloğu başlatmak için saccadometer düğmesine basın. </li><li> ilk blok tamamlandıktan sonra, ikinci bloktan önce bir dakika boşluk bırakın. 40 çalışmaların bir dizi oluşturmak için saccadometer Reset ve bir dakika boşluğu sonuna doğru, kırmızı nokta ters yönde mümkün olduğunca çabuk gözlerini taşımak için bir sonraki blok için katılımcıya talimat ve böyle olacağını açıklamak Bu 40 kere yapmak gerekecektir. sn Başlangıçdenemeler (Antisaccades) ve ond blok. </li><li> İkinci blokta tamamlanmasından sonra, bir daha 1 dk boşluk bırakın adım 3.5 talimatı tekrarlamak ve denemeler (Antisaccades) üçüncü blok başlar. </li><li> Üçüncü blok tamamlandıktan sonra, bir daha 1 dk boşluk bırakın adım 3.5 talimatı tekrarlamak ve denemeler (Antisaccades) dördüncü bloğu başlar. </li><li> Dördüncü blok tamamlandıktan sonra, bir daha 1 dk boşluk bırakın ve testlerin nihai bloğu için açıklamak bir tarafa veya ortadan atlayarak kırmızı nokta takip etmek kadar çabuk ve doğru bir şekilde gözlerini hareket etmelerini isteyin diğer, ilk bloğunda yaptığı tam olarak. </li><li> 60 çalışmaların bir dizi oluşturmak ve denemeler (Prosaccades) son bloğu başlatmak için saccadometer sıfırlayın. </li></ol><img alt="şekil 2" src="/files/ftp_upload/53640/53640fig2.jpg" /> Şekil 2. Eye Movement Görevler. Şematik illustratisakkadik görevlerden iki örnek göstermeye. Katı mavi nokta hedefi temsil ve noktalı mavi daire tespitin alanını temsil eder. SOL konu hedefe doğru bakmak istenir bir prosaccadic görevi gösterir. SAĞ konu görsel uyaranın uzak bakmak istenir bir antisaccade gösterir . Bu ters yönde sakkaddan daha doğal prosaccade tepkisi ve neslin engellenmesini gerektirir. <a href="https://www.jove.com/files/ftp_upload/53640/53640fig2large.jpg" target="_blank">Bu rakamın büyük halini görmek için lütfen buraya tıklayınız.</a> 4. Derin Beyin Stimülatör Ayarları Not: derin beyin uyarıcıları ile katılımcılar stimülatörü sistemi yani, normal olarak çalışan bugüne kadar testlerini, bir &#39;uyarılmasına&#39; veri seti elde edilmiştir. Test şimdi stimülatör sistemi (kapalı durumda tekrar edilmesi gerekirDBS sistemleri olmadan sağlıklı kontrol katılımcıları için bu bölümü) geçerli olmayacaktır. <ol><li> DBS sistemi kapatın. eğitimli bir klinik personeli tarafından bunu yapın. testten önce 30 dakika bekleyin. </li><li> Tam bir &#39;stimülasyon kapalı&#39; veri almak için - sakkadik test tekrarlayın (3.9 3.2 adımlar). </li><li> geri DBS sistemi (yine bu uygun şekilde eğitilmiş klinik personeli tarafından yapılmalıdır) açın. </li></ol> 5. Veri Analizi Not: derin beyin uyarıcıları ile katılımcılar stimülatörü sistemi yani, normal olarak çalışan bugüne kadar testlerini, bir &#39;uyarılmasına&#39; veri seti elde edilmiştir. Test şimdi stimülatör sistemi (bu bölüm geçerli olmayacaktır DBS sistemleri olmadan sağlıklı kontrol katılımcıları için) kapalı durumda tekrar edilmesi gerekir. <ol><li> analiz için bilgisayara saccadometer ham verileri indirin. </li><li> sakkadlar çarp dışlamak için saccadometer yazılım programını kullanınsakkadik gecikmeleri, zirve hızları ve genlikleri de dahil olmak üzere yanıp söner ve baş hareketleri, ve hesaplamak için değişkenler tarafından ted. Not: Aşırı baş hareketleri veya yanıp kirlenmiş kayıtlar otomatik olarak yazılım tarafından kaldırılır. <ol><li> gecikme ile az 80 milisaniye veya daha yüksek 1,000 milisaniye sakkadların çıkarın. Not: Sakkadik gecikme otomatik olarak hız ve ivme dayalı bir sakkaddan algılama algoritması kullanılarak hesaplanacaktır. sakkaddan başlangıcı göz hızı / sn 5 derecelik bir eşiği aştığında noktası olarak tanımlanır. </li></ol></li></ol>

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The authors have nothing to disclose.

kaliteli sakkadik verilerin elde edilmesinde en önemli faktör katılımcıya verilen talimatlar açık ve kesin olmasını sağlamaktır. antisaccadic görev için talimatları tam olarak açık değildir, örneğin, bir katılımcı yerine Prosaccades çalıştırmak için olasıdır. katılımcı açıkça uyaranlara göremiyorum veya saccadometer doğru göz pozisyonunu ölçmek olamaz eğer kayıtlar da şımarık olabilir. veriler düşük kalitede olması için görünen Böylece eğer deneyci Ortam ışığı ?...

Son yıllarda 1 yapma nöral karar üst düzey mekanizmaları hakkında bilgi almak için bir nicel ve non-invaziv bir yöntem olarak reaksiyon süreleri ölçümlerinin kullanımı artan ilgi olmuştur. kapsamlı olarak araştırılmıştır reaksiyon süresi bir tipi, Sakkadik gecikme olarak bilinen görsel uyaran, sunumu ile ilgili sakkad başlatmak için gereken zamandır. Sakkadlar hızla başka bir yerden bizim bakışları kayması meydana hızlı göz hareketleri vardır. Bunlar genellikle iki ya da üç saniyede bir frekansta meydana gelen biz yapmak göz hareketleri sık türüdür. Her sakkaddan etkisi başka 2 yerine görsel dünyada bir işaret bakmak için bir karardır. Göz hareketlerini kontrol nöral yolları yoğun çalışmalar yapılmış ve oldukça iyi 3 belgelenmiştir. Hassas elektronik ekipman kullanılarak, okülomotor fonksiyon yönleri hassas ve objectivel olabilirY miktarı. Bu göz hareketlerinin kendilerini detaylı bir çalışma kolaylaştırır ama aynı zamanda onları nörofizyoloji ve patofizyoloji diğer alanlarını araştırmak için bir araç olarak kullanılmasına izin verir. Göz hareketleri ölçüm hastalık durumları hakkında yararlı bilgiler sağlayabilir. Sakkadik göz hareketleri son zamanlarda, örneğin, Huntington 4,5 ve Parkinson hastalıkları 6,7 olmak üzere nörodejeneratif hastalıkların potansiyel biyomarkerların olarak çok dikkat aldık ve iyi sakkadik reaksiyon süreleri bu koşullarda normalden daha yavaş olma eğiliminde olduğu saptanmıştır. Sakkadik ölçüm potansiyel kullanımları hastalıkların teşhis ve izlemesi ile AİDS içerir. Sakkadik görevler gibi (görsel uyarana karşı tarafa mümkün olduğunca çabuk bakarak) antisaccade veya Bellek gibi daha karmaşık görevler için (bir aniden beliren görsel uyaranın doğru sağdan sola ya da mümkün olduğunca hızlı bir şekilde bakarak) basit prosaccade aralığı güdümlü sakkaddan (seyir) Artık orada bir hedefin hatırladı konuma doğru. Derin beyin stimülasyonu birkaç nörolojik durumlar için etkili bir tedavi yöntemidir. En çok titreme, kasılma, bradikinezi ve diskinezi dahil olmak üzere Parkinson hastalığı, motor semptomları tedavi etmek için kullanılır. Aynı zamanda, obsesif kompulsif bozukluk gibi daha az yaygın nöropatik ağrı, epilepsi ve psikiyatrik durumlar için distoni ve temel titreme ve da dahil olmak üzere başka hareket bozukluğu için kullanılmaktadır. Bu bilim adamları, in vivo insan beyninin derin yapılara direkt elektrik erişime sahip ve bu nedenle deneysel nöroloji için değerli bir fırsat sunduğu tek ayardır. hedeflerin çeşitli koşullarına bağlı olarak uyarılır Okülomotor yollarıyla ilgilidir çoğu bazal ganglion birkaç yerle de dahil olmak üzere, tedavi edilen. Bu çalışmalar çeşitli uyarım sunmak için DBS sistemi kullanılarak yapılabilir demektirBelirli bir beyin konumu ve bir göz izleme cihazına kaydetmek ve etkilerini analiz etmek. deneysel paradigma bağlı olarak, bu tür çalışmalar, bölgenin fizyolojisi hakkında bilgi uyarılmış olan hastalık veya hangi DBS o ortamda çalışan mekanizmanın etkilerini verebilir. Bu makalede, Derin Beyin Stimülasyonu hastalarında sakkadik göz hareketi testine genel bir yaklaşım anlatılmaktadır. göz izleme ekipmanları birkaç farklı türleri vardır. Bu protokol açıklanan araştırma için taşınabilir bir saccadometer yatay sakkadik göz hareketlerini kaydetmek için kullanıldı. Taşınabilir saccadometers oturumları özellikle ağır diskinezi ile muzdarip olanlar için, Parkinson hastalığı olan hastalar için daha rahat olduğu anlamına gelir Baş desteğini (Şekil 1), gerekmeyen avantajına sahiptir. Burada kullanılan saccadometer hafif ve yaklaşık 5 cm genişliğinde ve 10 cm boyunda. saccadometer measudoğrudan kızılötesi oculography kullanılarak res göz hareketleri: medial canthus kullanım ışığın önüne yerleştirilmiş bir kızıl ötesi kaynağı ve sensör milisaniye aralıklarla göz küresinin dönme pozisyonunu kurmak için kornea yansıyan. Analiz için kaliteli veri elde etmek için saccadometer en az 12 bit çözünürlükte en az 1 kHz&#39;lik bir hızda numune gerekir. Burada kullanılan saccadometer görsel uyaranlar tarafından üretilen ışığın üç kırmızı 13 cd m -2 noktalar vardı düşük güç lazerler inşa tek orta hatta spot ve ± 10 derece, diğer ikisi bazı 0,1 derece subtending her nokta (yani ,) sağa sol. <img alt="Şekil 1" src="/files/ftp_upload/53640/53640fig1.jpg" /> Şekil 1. Saccadometer. Kafa saccadometer bir elastik bant takılı ve burun köprüsü üzerinde dinlenme monte edilebilir. Dört minyatür lazerler görsel hedef projemat yüzeyi ve katılımcının göz hareketlerine ilgili her gözün burun tarafında farklı kızılötesi yansıma dönüştürücüler ile ölçülür. Lazer hedefleri baş hareket ettikçe, kafalıklar gerekli değildir. <a href="https://www.jove.com/files/ftp_upload/53640/53640fig1large.jpg" target="_blank">Bu rakamın büyük halini görmek için lütfen buraya tıklayınız.</a>

<table><tbody><tr><td>Saccadometer device</td><td>Ober Consulting Poland</td><td></td><td></td></tr><tr><td>Computer with Windows environment</td><td></td><td></td><td></td></tr><tr><td>Software, Latency Meter for downloading the raw data from the saccadometer</td><td></td><td></td><td></td></tr></tbody></table>

using saccadometry with deep brain stimulation to study normal and pathological brain function

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology.

Şekil 3, implante subtalamik çekirdeği DBS sistemi ile Parkinson hastalığı hastadan, sakkadik göz hareketi yörüngeleri bir örneğini göstermektedir. stimülatör sistem kapalı (üst grafik) ve (alt grafik) açık olan iki grafik hastanın Prosaccades arsa. Grafikler Her iz uzaklıkta orta hat (Y ekseni) derece göz pozisyonu, zamanın bir fonksiyonu olarak değiştiği, bir tek sakkaddan örneğin, (x ekseni) yörüngesini gösterir. Hem sola ve sağ...

Watch this Scientific Journal Video about Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function at JoVE.com

Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

Derin Beyin Uyarım ile Saccadometry kullanarak normal ve patolojik beyin fonksiyonlarını incelemek için

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including ...

using-saccadometry-with-deep-brain-stimulation-to-study-normal

Research

JoVE Journal

Medicine

7.4K Görüntüleme.  The University of Oxford. This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

Video: Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through implanted electrodes. Deep brain stimulation was first implemented as a therapeutic modality by Benabid et al. in the late 1980s, when he used this technique to stimulate the ventral intermediate nucleus of the thalamus for the treatment of tremor 1. Currently, the procedure is used to treat patients who fail to respond adequately to medical management for diseases such as Parkinson's, dystonia, and essential tremor. The efficacy of this procedure for the treatment of Parkinson's disease has been demonstrated in well-powered, randomized controlled trials 2. Presently, the U.S. Food and Drug Administration has approved DBS as a treatment for patients with medically refractory essential tremor, Parkinson's disease, and dystonia. Additionally, DBS is currently being evaluated for the treatment of other psychiatric and neurological disorders, such as obsessive compulsive disorder, major depressive disorder, and epilepsy. 
DBS has not only been shown to help people by improving their quality of life, it also provides researchers with the unique opportunity to study and understand the human brain. Microelectrode recordings are routinely performed during DBS surgery in order to enhance the precision of anatomical targeting. Firing patterns of individual neurons can therefore be recorded while the subject performs a behavioral task. Early studies using these data focused on descriptive aspects, including firing and burst rates, and frequency modulation 3. More recent studies have focused on cognitive aspects of behavior in relation to neuronal activity 4,5. This article will provide a description of the intra-operative methods used to perform behavioral tasks and record neuronal data with awake patients during DBS cases. Our exposition of the process of acquiring electrophysiological data will illuminate the current scope and limitations of intra-operative human experiments.

Deep brain stimulation surgery offers a unique opportunity to examine information encoding in the awake human brain. This article will describe intra-operative methods used to perform cognitive and behavioral tasks while simultaneously acquiring physiological data such as EMG, single-unit neuronal activity and/or local field potentials.

Derin beyin stimülasyonu Cerrahi Uygulanan Uyanık İnsanlar İntraoperatif Davranış Görevler

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through ...

Tıp

Combined Invasive Subcortical and Non-invasive Surface Neurophysiological Recordings for the Assessment of Cognitive and Emotional Functions in Humans

In spite of the success in applying non-invasive electroencephalography (EEG), magneto-encephalography (MEG) and functional magnetic resonance imaging (fMRI) for extracting crucial information about the mechanism of the human brain, such methods remain insufficient to provide information about physiological processes reflecting cognitive and emotional functions at the subcortical level. In this respect, modern invasive clinical approaches in humans, such as deep brain stimulation (DBS), offer a tremendous possibility to record subcortical brain activity, namely local field potentials (LFPs) representing coherent activity of neural assemblies from localized basal ganglia or thalamic regions. Notwithstanding the fact that invasive approaches in humans are applied only after medical indication and thus recorded data correspond to altered brain circuits, valuable insight can be gained regarding the presence of intact brain functions in relation to brain oscillatory activity and the pathophysiology of disorders in response to experimental cognitive paradigms. In this direction, a growing number of DBS studies in patients with Parkinson&#39;s disease (PD) target not only motor functions but also higher level processes such as emotions, decision-making, attention, memory and sensory perception. Recent clinical trials also emphasize the role of DBS as an alternative treatment in neuropsychiatric disorders ranging from obsessive compulsive disorder (OCD) to chronic disorders of consciousness (DOC). Consequently, we focus on the use of combined invasive (LFP) and non-invasive (EEG) human brain recordings in assessing the role of cortical-subcortical structures in cognitive and emotional processing trough experimental paradigms (e.g. speech stimuli with emotional connotation or paradigms of cognitive control such as the Flanker task), for patients undergoing DBS treatment.

The present protocol aims at assessing cognitive-emotional functions in the basal ganglia by simultaneous neurophysiological recording of local field potentials and non-invasive brain cortical activity (EEG). The procedure is exemplified by the use of paradigms involving speech stimuli with emotional connotation or the Flanker task involving cognitive control.

İnsanlarda Kombine İnvaziv subkortikal ve Bilişsel Değerlendirme Non-invaziv Yüzey Nörofizyolojik Kayıtlar ve Duygusal Fonksiyonlar

In spite of the success in applying non-invasive electroencephalography (EEG), magneto-encephalography (MEG) and functional magnetic resonance imaging ...

Davranış

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson&#39;s lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way.

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

Merdiven ve Silindir Testi: Yeni Bir Yaklaşım Hemiparkinsonian Rat Derin beyin stimülasyonu Etkileri Motor Sonuçlarını Değerlendirmek için

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson&#39;s disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.
Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson&#39;s Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.

Adaptive deep brain stimulation (aDBS) is effective for Parkinson&#8217;s disease, improving symptoms and reducing power consumption compared to conventional deep brain stimulation (cDBS). In aDBS we track a local field potential biomarker (beta oscillatory amplitude) in real time and use this to control the timing of stimulation.

Adaptif Derin Beyin Stimülasyonu İle Parkinson Hastalığı kontrol

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time ...

Deep Brain Stimulation with Simultaneous fMRI in Rodents

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to image rodents with simultaneous DBS. DBS fMRI presents a number of technical challenges, including accuracy of electrode implantation, MR artifacts created by the electrode, choice of anesthesia and paralytic to minimize any neuronal effects while simultaneously eliminating animal motion, and maintenance of physiological parameters, deviation from which can confound the BOLD signal.&#160;Our laboratory has developed a set of procedures that are capable of overcoming most of these possible issues. For electrical stimulation, a homemade tungsten bipolar microelectrode is used, inserted stereotactically at the stimulation site in the anesthetized subject. In preparation for imaging, rodents are fixed on a plastic headpiece and transferred to the magnet bore. For sedation and paralysis during scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused, along with a minimal dose of isoflurane; this preparation minimizes the BOLD ceiling effect of volatile anesthetics. In this example experiment, stimulation of the subthalamic nucleus (STN) produces BOLD responses which are observed primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous DBS and fMRI allows the unambiguous modulation of neural circuits dependent on stimulation location and stimulation parameters, and permits observation of neuronal modulations free of regional bias. This technique may be used to explore the downstream effects of modulating neural circuitry at nearly any brain region, with implications for both experimental and clinical DBS.

This protocol describes a standard method for simultaneous functional magnetic resonance imaging and deep brain stimulation in the rodent. The combined use of these experimental tools allows for the exploration of global downstream activity in response to electrical stimulation at virtually any brain target.

Kemirgenler Eşzamanlı fMRI ile derin beyin stimülasyonu

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for ...

Nörobilim

Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective treatment for several movement disorders that have failed to respond to medication. Recent progress in the field of DBS surgery has begun to extend the application of this surgical technique to other conditions as diverse as morbid obesity, depression and obsessive compulsive disorder. Despite these expanding indications, little is known about the underlying physiological mechanisms that facilitate the beneficial effects of DBS surgery. One approach to this question is to perform gene expression analysis in neurons that receive the electrical stimulation. Previous studies have shown that neurogenesis in the rat dentate gyrus is elicited in DBS targeting of the anterior nucleus of the thalamus1. DBS surgery targeting the ATN is used widely for treatment refractory epilepsy. It is thus of much interest for us to explore the transcriptional changes induced by electrically stimulating the ATN. In this manuscript, we describe our methodologies for stereotactically-guided DBS surgery targeting the ATN in adult male Wistar rats. We also discuss the subsequent steps for tissue dissection, RNA isolation, cDNA preparation and quantitative RT-PCR for measuring gene expression changes. This method could be applied and modified for stimulating the basal ganglia and other regions of the brain commonly clinically targeted. The gene expression study described here assumes a candidate target gene approach for discovering molecular players that could be directing the mechanism for DBS.

The mechanism underlying the therapeutic effects of Deep Brain Stimulation (DBS) surgery needs investigation. The methods presented in this manuscript describe an experimental approach to examine the cellular events triggered by DBS by analyzing the gene expression profile of candidate genes that can facilitate neurogenesis post DBS surgery.

Ön Talamusun Çekirdek Derin Beyin Stimülasyon sonra Sıçan Hippocampus Gen İfade Değişim Analizi

Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective ...

Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, dystonia or tremor. DBS is based on the delivery of electrical stimuli to specific deep anatomic structures of the central nervous system. However, the mechanisms underlying the effect of DBS remain enigmatic. This has led to an interest in investigating the impact of DBS in animal models, especially in rats. As DBS is a long-term therapy, research should be focused on molecular-genetic changes of neural circuits that occur several weeks after DBS. Long-term DBS in rats is challenging because the rats move around in their cage, which causes problems in keeping in place the wire leading from the head of the animal to the stimulator. Furthermore, target structures for stimulation in the rat brain are small and therefore electrodes cannot easily be placed at the required position. Thus, a set-up for long-lasting stimulation of rats using platinum/iridium electrodes with an impedance of about 1 M&#937; was developed for this study. An electrode with these specifications allows for not only adequate stimulation but also recording of deep brain structures to identify the target area for DBS. In our set-up, an electrode with a plug for the wire was embedded in dental cement with four anchoring screws secured onto the skull. The wire from the plug to the stimulator was protected by a stainless-steel spring. A swivel was connected to the circuit to prevent the wire from becoming tangled. Overall, this stimulation set-up offers a high degree of free mobility for the rat and enables the head plug, as well as the wire connection between the plug and the stimulator, to retain long-lasting strength.

A method for implanting electrodes into the subthalamic nucleus (STN) of rats is described. Better localization of the STN was achieved by using a microrecording system. Furthermore, a stimulation set-up is presented that is characterized by long-lasting connections between the head of the animal and the stimulator.

Mikroelektrod Uzun vadeli Derin Beyin Stimülasyonu için Sıçan Subtalamik Nucleus içine elektrotlar implantasyonu Rehberli

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, ...

Targeting Neuronal Fiber Tracts for Deep Brain Stimulation Therapy Using Interactive, Patient-Specific Models

Deep brain stimulation (DBS), which involves insertion of an electrode to deliver stimulation to a localized brain region, is an established therapy for movement disorders and is being applied to a growing number of disorders. Computational modeling has been successfully used to predict the clinical effects of DBS; however, there is a need for novel modeling techniques to keep pace with the growing complexity of DBS devices. These models also need to generate predictions quickly and accurately. The goal of this project is to develop an image processing pipeline to incorporate structural magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) into an interactive, patient specific model to simulate the effects of DBS. A virtual DBS lead can be placed inside of the patient model, along with active contacts and stimulation settings, where changes in lead position or orientation generate a new finite element mesh and solution of the bioelectric field problem in near real-time, a timespan of approximately 10 seconds. This system also enables the simulation of multiple leads in close proximity to allow for current steering by varying anodes and cathodes on different leads. The techniques presented in this paper reduce the burden of generating and using computational models while providing meaningful feedback about the effects of electrode position, electrode design, and stimulation configurations to researchers or clinicians who may not be modeling experts.

The goal of this project is to develop an interactive, patient-specific modeling pipeline to simulate the effects of deep brain stimulation in near real-time and provide meaningful feedback as to how these devices influence neural activity in the brain.

Etkileşimli, hastanın özel modelleri kullanarak derin beyin stimülasyonu tedavisi için nöronal Fiber yolları hedefleme

Deep brain stimulation (DBS), which involves insertion of an electrode to deliver stimulation to a localized brain region, is an established therapy for ...

Biyomühendislik

Acute In Vivo Electrophysiological Recordings of Local Field Potentials and Multi-unit Activity from the Hyperdirect Pathway in Anesthetized Rats

Converging evidence shows that many neuropsychiatric diseases should be understood as disorders of large-scale neuronal networks. To better understand the pathophysiological basis of these diseases, it is necessary to precisely characterize in which way the processing of information is disturbed between the different neuronal parts of the circuit. Using extracellular in vivo electrophysiological recordings, it is possible to accurately delineate neuronal activity within a neuronal network. The application of this method has several advantages over alternative techniques, e.g., functional magnetic resonance imaging and calcium imaging, as it allows a unique temporal and spatial resolution and does not rely on genetically engineered organisms. However, the use of extracellular in vivo recordings is limited since it is an invasive technique that cannot be universally applied. In this article, a simple and easy to use method is presented with which it is possible to simultaneously record extracellular potentials such as local field potentials and multiunit activity at multiple sites of a network. It is detailed how a precise targeting of subcortical nuclei can be achieved using a combination of stereotactic surgery and online analysis of multi-unit recordings. Thus, it is demonstrated, how a complete network such as the hyperdirect cortico-basal ganglia loop can be studied in anesthetized animals in vivo.

Acute In Vivo Electrophysiological Recordings of Local Field Potentials and Multi-unit Activity from the Hyperdirect Pathway in Anesthetized Rats

In this study, the methodology is presented on how to perform multi-site in vivo electrophysiological recordings from the hyperdirect pathway under urethane anesthesia.

Akut<emIn vivo</em&gt; Anestezi Uygulanan Sıçanlarda Hiperdirect Pathway&#39;den Lokal Alan Potansiyellerinin Elektrofizyolojik Kayıtları ve Çoklu Ünite Aktivitesi

Converging evidence shows that many neuropsychiatric diseases should be understood as disorders of large-scale neuronal networks. To better understand the ...

An Invasive Method for the Activation of the Mouse Dentate Gyrus by High-frequency Stimulation

Electrical high-frequency stimulation (HFS), using implanted electrodes targeting various brain regions, has been proven as an effective treatment for various neurological and psychiatric disorders. HFS in the deep region of the brain, also named deep-brain stimulation (DBS), is becoming increasingly important in clinical trials. Recent progress in the field of high-frequency DBS (HF-DBS) surgery has begun to spread the possibility of utilizing this invasive technique to other situations, such as treatment for major depression disorder (MDD), obsessive-compulsive disorder (OCD), and so on. 
Despite these expanding indications, the underlying mechanisms of the beneficial effects of HF-DBS remain enigmatic. To address this question, one approach is to use implanted electrodes that sparsely activate distributed subpopulations of neurons by HFS. It has been reported that HFS in the anterior nucleus of the thalamus could be used for the treatment of refractory epilepsy in the clinic. The underlying mechanisms might be related to the increased neurogenesis and altered neuronal activity. Therefore, we are interested in exploring the physiological alterations by the detection of neuronal activity as well as neurogenesis in the mouse dentate gyrus (DG) before and after HFS treatment. 
In this manuscript, we describe methodologies for HFS to target the activation of the DG in mice, directly or indirectly and in an acute or chronic manner. In addition, we describe a detailed protocol for the preparation of brain slices for c-fos and Notch1 immunofluorescent staining to monitor the neuronal activity and signaling activation and for bromodeoxyuridine (BrdU) labeling to determine the neurogenesis after the HF-DBS induction. The activation of the neuronal activity and neurogenesis after the HF-DBS treatment provides direct neurobiological evidence and potential therapeutic benefits. Particularly, this methodology can be modified and applied to target other interested brain regions such as the basal ganglia and subthalamic regions for specific brain disorders in the clinic.

This protocol shows how to set up a reliable HFS method in mice. Neurons throughout the hippocampal dentate gyrus are electrically stimulated by HFS directly and indirectly in vivo. Neuronal activity and molecular signaling are examined by c-fos and Notch1 immunofluorescent staining, respectively; neurogenesis is quantified by bromodeoxyuridine labeling assay.

Yüksek frekanslı stimülasyon tarafından fare dentat Gyrus aktivasyonu için invaziv bir yöntem

Electrical high-frequency stimulation (HFS), using implanted electrodes targeting various brain regions, has been proven as an effective treatment for ...