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.

Il comitato etico locale ha approvato questo studio e ha informato acconsentì è stato ottenuto dai partecipanti come indicato di seguito nella sezione 1. 1. partecipante Consenso <ol><li> Fornire ai partecipanti un foglio informativo che spiega in modo dettagliato cosa la sessione di test includerà. </li><li> Dopo che i partecipanti hanno la possibilità di leggere e discutere tutte le domande, dubbi o altre questioni legate alla loro parte presa in studio, passare attraverso il modulo di consenso con loro, spiegando ogni punto il modulo di consenso e dando loro la possibilità di fare tutte le domande potrebbero avere. Chiedi ai partecipanti di compilare il modulo. </li></ol> 2. Impostazione del Saccadometer <ol><li> Posizionare il dispositivo sulla testa del paziente, garantito da una cinghia elastica regolabile e appoggiato sul dorso del naso. Poiché gli stimoli muovono esattamente con la testa, senza appoggiatesta è necessario e il dispositivo è comodo da wear. </li><li> Chiedere al paziente di sedersi a 1,5 m da uno schermo opaco piatta. </li><li> Assicurarsi che la luce ambiente è debole in modo che gli stimoli (punti luce rossa) si vedono chiaramente. </li></ol> 3. registrazione di una sessione saccadici Nota: Per fare un esempio un protocollo standard che mette alla prova sia prosaccades e antisaccades 8 è descritto qui. Questo protocollo si compone di cinque blocchi: 60 prosaccades, 40 antisaccades x 3, e 60 prosaccades con una pausa di 1 minuto tra i blocchi. La seduta dura circa 40 min. <ol><li> Impostare il saccadometer modo che per ogni prova viene visualizzata la porta fissazione centrale per un casuale fore periodo di 1,0 - 2,0 sec, dopo di che si spegne e uno dei bersagli periferici appare, in modo casuale a destra oa sinistra 9. Nota: I tre obiettivi sono macchie di luce rossa proiettata sullo schermo di fronte al partecipante (vedi 2.2) da una bassa potenza laser integrati nel saccadometer. L&#39;aut saccadometerinterruttori omatically i laser e si spegne alla visualizzazione / spegnere gli obiettivi nella sequenza necessaria. </li><li> Istruire il partecipante che il test è composto da cinque blocchi con una pausa di un minuto tra i blocchi. </li><li> Prima del primo blocco istruire il partecipante di spostare i loro occhi più rapidamente e accuratamente possibile seguire il punto rosso saltando dal centro verso un lato o l&#39;altro e indicare loro di fare questo 60 volte. </li><li> Impostare la saccadometer per generare una sequenza di 60 prove. Premere il pulsante sulla saccadometer per avviare il primo blocco di prove (prosaccades). </li><li> Dopo il completamento del primo blocco, lasciare uno spazio un minuto prima del secondo blocco. Ripristinare il saccadometer per generare una sequenza di 40 studi, e verso la fine del un&#39;intercapedine minuti, istruire il partecipante per il blocco successivo di spostare i loro occhi più rapidamente possibile nella direzione opposta al punto rosso, e spiega che faranno essere richiesto di fare questo 40 volte. Avviare il secblocco OND di prove (antisaccades). </li><li> Dopo il completamento del secondo blocco, lasciare un ulteriore 1 min gap, ripetere l&#39;istruzione in fase 3.5 e avviare il terzo blocco di prove (antisaccades). </li><li> Dopo il completamento del terzo blocco, lasciare un ulteriore 1 min gap, ripetere l&#39;istruzione in fase 3.5 e avviare il quarto blocco di prove (antisaccades). </li><li> Dopo il completamento del quarto blocco, lasciare un ulteriore 1 min gap, e spiega che per il blocco finale di test chiedere ai partecipanti di spostare i loro occhi più rapidamente e accuratamente possibile seguire il punto rosso saltando dal centro verso un lato o altri, esattamente come nel primo blocco. </li><li> Ripristinare il saccadometer per generare una sequenza di 60 prove, e avviare il blocco finale di prove (prosaccades). </li></ol><img alt="figura 2" src="/files/ftp_upload/53640/53640fig2.jpg" /> Figura 2. Operazioni di movimento degli occhi. Illustrati schematicisulla mostra due esempi di attività saccadici. Lo spot blu continua rappresenta il bersaglio e il cerchio blu tratteggiata rappresenta l&#39;area di fissaggio. Sinistra mostra un compito prosaccadic in cui il soggetto viene chiesto di guardare verso il bersaglio. A destra mostra un antisaccade in cui si chiede al soggetto di distogliere lo sguardo dallo stimolo visivo . Ciò richiede l&#39;inibizione della risposta prosaccade più naturale e generazione di una saccade in direzione opposta. <a href="https://www.jove.com/files/ftp_upload/53640/53640fig2large.jpg" target="_blank">Si prega di cliccare qui per vedere una versione più grande di questa figura.</a> 4. Impostazioni stimolatore cerebrale profonda Nota: per i partecipanti con stimolatori cerebrali profondi condurre i test finora con sistema stimolatore esecuzione come normale, vale a dire, un set di dati &#39;sulla stimolazione&#39; è stato ottenuto. Test ora deve essere ripetuta con il sistema stimolatore spento (per i partecipanti di controllo sani, senza sistemi di DBS non si applica questa sezione). <ol><li> Spegnere il sistema DBS off. A tale scopo, un personale clinico addestrato. Lasciare 30 minuti prima del test. </li><li> Ripetere il test saccadico (passi 3,2-3,9) per ottenere un &#39;off stimolazione&#39; set di dati completo. </li><li> Accendere il sistema DBS indietro (anche questo dovrebbe essere fatto da personale clinico adeguatamente formato). </li></ol> Analisi 5. I dati Nota: per i partecipanti con stimolatori cerebrali profondi condurre i test finora con sistema stimolatore esecuzione come normale, vale a dire, un set di dati &#39;sulla stimolazione&#39; è stato ottenuto. Test ora deve essere ripetuta con il sistema stimolatore spento (per i partecipanti sani di controllo senza sistemi di DBS questa sezione non si applica). <ol><li> Scarica i dati grezzi dal saccadometer ad un computer per l&#39;analisi. </li><li> Utilizzare il programma software del saccadometer di escludere saccades distorsioneTed lampeggia e movimenti della testa, e per calcolare le variabili tra cui latenze saccadici, velocità di picco, e ampiezze. Nota: Records contaminati da movimenti della testa eccessivi o lampeggia vengono rimossi automaticamente dal software. <ol><li> Rimuovere saccades con una latenza inferiore a 80 msec o superiore a 1.000 msec. Nota: la latenza saccadici viene calcolata automaticamente utilizzando un algoritmo di saccade di rilevamento sulla base di velocità e accelerazione. L&#39;insorgenza di una saccade è identificato come il punto in cui la velocità dell&#39;occhio supera una soglia di 5 gradi / sec. </li></ol></li></ol>

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The authors have nothing to disclose.

Il fattore più critico per ottenere dati di buona qualità saccadico è garantire che le istruzioni date al partecipante sono chiare e precise. Ad esempio, se le istruzioni per l&#39;attività antisaccadic non sono completamente chiare, il partecipante è probabile eseguire prosaccades invece. Le registrazioni possono anche essere viziato, se il partecipante non può vedere chiaramente gli stimoli o il saccadometer non può misurare con precisione la posizione degli occhi. Pertanto, se i dati sembrano essere di bassa q...

Negli ultimi anni c&#39;è stato un crescente interesse per l&#39;uso di misure di tempi di reazione come un modo quantitativo e non invasivo di ottenere informazioni sui meccanismi alto livello di decisione neurale facendo 1. Un tipo di tempo di reazione che è stato ampiamente studiato è il tempo necessario per avviare un saccade su presentazione di uno stimolo visivo, noto come latenza saccadico. Saccades sono i movimenti oculari rapidi che si verificano quando ci spostiamo rapidamente lo sguardo da un luogo all&#39;altro. Essi sono il tipo più comune di movimenti oculari facciamo, che si verificano ad una frequenza di tipicamente due o tre al secondo. Ogni saccade è in effetti una decisione a guardare uno spunto nel mondo visivo piuttosto che un altro 2. I percorsi neurali che controllano i movimenti oculari sono stati ampiamente studiati e sono abbastanza ben documentati 3. Utilizzando apparecchiature elettroniche sensibili, aspetti della funzione oculomotor possono essere preciso e objectively quantificato. Questo facilita lo studio dettagliato dei movimenti oculari stessi, ma consente anche loro di essere utilizzati come strumento per indagare su altre aree della neurofisiologia e fisiopatologia. misura il movimento degli occhi può fornire informazioni utili su stati di malattia. Movimenti oculari saccadici hanno recentemente, per esempio, ha ricevuto molta attenzione come potenziale biomarker in patologie neurodegenerative tra cui il morbo di Huntington e Parkinson 4,5 6,7, ed è ben stabilito che i tempi di reazione saccadici tendono ad essere più lenta del normale in queste condizioni. I potenziali usi di misura saccadico includono un aiuto per la diagnosi e il monitoraggio della malattia. compiti saccadici vanno dal semplice prosaccade (guardando il più rapidamente possibile verso uno stimolo visivo improvvisamente appare a sinistra o destra) per compiti più complessi come la antisaccade (guardando il più rapidamente possibile al lato opposto ad uno stimolo visivo) o Memory saccade guidata (guardandoverso la posizione ricordato di un bersaglio che non c&#39;è più). la stimolazione cerebrale profonda è un trattamento efficace per diverse condizioni neurologiche. E &#39;più comunemente usato per trattare i sintomi motori della malattia di Parkinson tra cui tremore, rigidità, bradicinesia, e discinesia. E &#39;utilizzato anche per altri disturbi del movimento, tra cui distonia e tremore essenziale, e meno comunemente per il dolore neuropatico, epilessia, e condizioni psichiatriche come il disturbo ossessivo compulsivo. E &#39;l&#39;unico ambiente in cui gli scienziati hanno accesso elettrico diretto alle strutture profonde del cervello umano in vivo e offre quindi una preziosa opportunità per la neurologia sperimentale. Una varietà di obiettivi vengono stimolati a seconda delle condizioni da trattare, tra cui diverse località nei gangli della base, molti dei quali sono coinvolti in percorsi oculomotori. Ciò significa che una vasta gamma di studi può essere effettuato utilizzando il sistema DBS trasportare lo stimoload un determinato luogo del cervello e un dispositivo di tracciamento oculare per registrare e analizzare i suoi effetti. Secondo il paradigma sperimentale, tali studi possono fornire informazioni sulla fisiologia della regione stimolata, gli effetti della malattia, o il meccanismo con cui DBS sta lavorando in quel particolare impostazione. Questo articolo descrive un approccio generale alla saccadico test movimento degli occhi in pazienti stimolazione cerebrale profonda. Diversi tipi di apparecchiature di tracciamento dell&#39;occhio sono disponibili. Per la ricerca descritta in questo protocollo un saccadometer portatile è stato utilizzato per registrare i movimenti oculari saccadici orizzontali. Saccadometers portatili hanno il vantaggio di non richiedere poggiatesta (vedi figura 1), il che significa che le sessioni sono più confortevoli per i pazienti con malattia di Parkinson, in particolare per coloro che soffrono di gravi discinesie. Il saccadometer usato qui è leggero e larga circa 5 cm e alto 10 cm. Il measu saccadometerres movimenti oculari mediante l&#39;uso di oculografia diretta a infrarossi: una sorgente di raggi infrarossi e sensore posizionato davanti alla luce dell&#39;uso canto mediale riflessa dalla cornea per stabilire la posizione di rotazione del bulbo oculare a intervalli millisecondo. Al fine di acquisire dati di buona qualità per l&#39;analisi del saccadometer dovrebbe campione ad una velocità di almeno 1 kHz con almeno risoluzione a 12 bit. Nella saccadometer qui utilizzato stimoli visivi erano tre rossi 13 cd m -2 macchie di luce prodotta da incasso in laser a bassa potenza, ogni spot sottendono alcuni 0,1 gradi, con un punto sulla linea mediana e le altre due a ± 10 gradi (cioè , a destra ea sinistra). <img alt="Figura 1" src="/files/ftp_upload/53640/53640fig1.jpg" /> Figura 1. Il Saccadometer. Testa montata saccadometer collegato a un elastico e di riposo sul ponte del naso. Quattro laser in miniatura progetto di destinazione visivas su una superficie opaca, e movimenti dell&#39;occhio del partecipante è misurato a differenziali trasduttori riflettanza all&#39;infrarosso sul lato nasale ciascun occhio. Come gli obiettivi del laser si muovono con la testa, poggiatesta non sono necessari. <a href="https://www.jove.com/files/ftp_upload/53640/53640fig1large.jpg" target="_blank">Cliccate qui per vedere una versione più grande di questa figura.</a>

<table border="0" cellpadding="0" cellspacing="0" width="88">
	<tbody>
		<tr>
			<td>Saccadometer device ( Ober Consulting Poland)</td>
		</tr>
		<tr>
			<td>Computer with Windows environment</td>
		</tr>
		<tr>
			<td>Software, Latency Meter for downloading the raw data from the saccadometer.</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.

La Figura 3 mostra un esempio di saccadici traiettorie dei movimenti oculari, da paziente morbo di Parkinson con un nucleo di sistema DBS subtalamico impiantato. I due grafici tracciano prosaccades del paziente con il sistema stimolatore spento (grafico superiore) e inserita (grafico inferiore). Ciascuna traccia diagrammi mostra la traiettoria di un singolo saccade, cioè, come la posizione dell&#39;occhio in gradi di distanza dalla linea mediana (asse y) varia ...

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.

Utilizzando Saccadometry con stimolazione cerebrale profonda per studiare normali e patologiche funzione cerebrale

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

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7.4K Views.  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.

Compiti del comportamento Intra-Operative negli esseri umani sottoposti a profonda Awake Surgery Brain Stimulation

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

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Medicina

Eye Tracking Young Children with Autism

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a direct, detailed and objective measure of gaze behavior, eye-tracking has become a valuable tool for examining abnormal perceptual strategies in clinical populations and has been used to identify disorder-specific characteristics1, promote early identification2, and inform treatment3. In particular, investigators of autism spectrum disorders (ASD) have benefited from integrating eye-tracking into their research paradigms4-7. Eye-tracking has largely been used in these studies to reveal mechanisms underlying impaired task performance8 and abnormal brain functioning9, particularly during the processing of social information1,10-11. While older children and adults with ASD comprise the preponderance of research in this area, eye-tracking may be especially useful for studying young children with the disorder as it offers a non-invasive tool for assessing and quantifying early-emerging developmental abnormalities2,12-13. Implementing eye-tracking with young children with ASD, however, is associated with a number of unique challenges, including issues with compliant behavior resulting from specific task demands and disorder-related psychosocial considerations. In this protocol, we detail methodological considerations for optimizing research design, data acquisition and psychometric analysis while eye-tracking young children with ASD. The provided recommendations are also designed to be more broadly applicable for eye-tracking children with other developmental disabilities. By offering guidelines for best practices in these areas based upon lessons derived from our own work, we hope to help other investigators make sound research design and analysis choices while avoiding common pitfalls that can compromise data acquisition while eye-tracking young children with ASD or other developmental difficulties.

Eye tracking has long been used to study gaze patterns in typically-developing individuals, but recent technological advancements have made its use with clinical populations, including autism, more feasible. While eye-tracking young children with autism can offer insight into early symptom manifestations, it involves methodological challenges. Suggestions for best practices are provided.

Eye tracking bambini piccoli con autismo

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a ...

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain

The central event in the pathogenesis of prion diseases involves a conversion of the host-encoded cellular prion protein PrPC into its pathogenic isoform PrPSc 1. PrPC is detergent-soluble and sensitive to proteinase K (PK)-digestion, whereas PrPSc forms detergent-insoluble aggregates and is partially resistant to PK2-6. The conversion of PrPC to PrPSc is known to involve a conformational transition of &alpha;-helical to &beta;-sheet structures of the protein. However, the in vivo pathway is still poorly understood. A tentative endogenous PrPSc, intermediate PrP* or "silent prion", has yet to be identified in the uninfected brain7.
Using a combination of biophysical and biochemical approaches, we identified insoluble PrPC aggregates (designated iPrPC) from uninfected mammalian brains and cultured neuronal cells8, 9. Here, we describe detailed procedures of these methods, including ultracentrifugation in detergent buffer, sucrose step gradient sedimentation, size exclusion chromatography, iPrP enrichment by gene 5 protein (g5p) that specifically bind to structurally altered PrP forms10, and PK-treatment. The combination of these approaches isolates not only insoluble PrPSc and PrPC aggregates but also soluble PrPC oligomers from the normal human brain. Since the protocols described here have been used to isolate both PrPSc from infected brains and iPrPC from uninfected brains, they provide us with an opportunity to compare differences in physicochemical features, neurotoxicity, and infectivity between the two isoforms. Such a study will greatly improve our understanding of the infectious proteinaceous pathogens. The physiology and pathophysiology of iPrPC are unclear at present. Notably, in a newly-identified human prion disease termed variably protease-sensitive prionopathy, we found a new PrPSc that shares the immunoreactive behavior and fragmentation with iPrPC 11, 12. Moreover, we recently demonstrated that iPrPC is the main species that interacts with amyloid-&beta; protein in Alzheimer disease13. In the same study, these methods were used to isolate Abeta aggregates and oligomers in Alzheimer's disease13, suggesting their application to non-prion protein aggregates involved in other neurodegenerative disorders.

A new species of cellular prion protein (PrPC) has recently been identified in uninfected human brains using the methods described here. These methods can be used to isolate various PrP species, while some of them are also useful in isolating other misfolded protein aggregates from human brains.

Isolamento di oligomeri PrP solubili e insolubili nel cervello umano normale

The central event in the pathogenesis of prion diseases involves a conversion of the host-encoded cellular prion protein PrPC into its pathogenic isoform ...

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

We have successfully integrated previously established Intracranial window (ICW) technology 1-4 with intravital 2-photon confocal microscopy to develop a novel platform that allows for direct long-term visualization of tissue structure changes intracranially. Imaging at a single cell resolution in a real-time fashion provides supplementary dynamic information beyond that provided by standard end-point histological analysis, which looks solely at 'snap-shot' cross sections of tissue.
Establishing this intravital imaging technique in fluorescent chimeric mice, we are able to image four fluorescent channels simultaneously. By incorporating fluorescently labeled cells, such as GFP+ bone marrow, it is possible to track the fate of these cells studying their long-term migration, integration and differentiation within tissue. Further integration of a secondary reporter cell, such as an mCherry glioma tumor line, allows for characterization of cell:cell interactions. Structural changes in the tissue microenvironment can be highlighted through the addition of intra-vital dyes and antibodies, for example CD31 tagged antibodies and Dextran molecules.
Moreover, we describe the combination of our ICW imaging model with a small animal micro-irradiator that provides stereotactic irradiation, creating a platform through which the dynamic tissue changes that occur following the administration of ionizing irradiation can be assessed.
Current limitations of our model include penetrance of the microscope, which is limited to a depth of up to 900 &mu;m from the sub cortical surface, limiting imaging to the dorsal axis of the brain. The presence of the skull bone makes the ICW a more challenging technical procedure, compared to the more established and utilized chamber models currently used to study mammary tissue and fat pads 5-7. In addition, the ICW provides many challenges when optimizing the imaging.

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

We describe a novel in vivo imaging technique that couples fluorescent chimeric mice with intracranial windows and high-resolution 2-photon microscopy. This imaging platform aids studies of dynamic changes in brain tissue and microvasculature, at a single-cell level, following pathological insults and is adaptable to assess intracranial drug delivery and distribution.

Un romanzo ad alta risoluzione<em&gt; In vivo</em&gt; Tecnica di imaging per studiare la risposta dinamica di strutture intracraniche alla crescita del tumore e Terapeutica

We have successfully integrated previously established Intracranial window (ICW) technology 1-4 with intravital 2-photon confocal microscopy to develop a ...

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are exacerbated when significant brain atrophy and age-related white matter changes (e.g. Leukoaraiosis) are present. Lesion Explorer (LE) is an accurate and reliable neuroimaging pipeline specifically developed to address such issues commonly observed on MRI of Alzheimer's disease and normal elderly. The pipeline is a complex set of semi-automatic procedures which has been previously validated in a series of internal and external reliability tests1,2. However, LE's accuracy and reliability is highly dependent on properly trained manual operators to execute commands, identify distinct anatomical landmarks, and manually edit/verify various computer-generated segmentation outputs.
LE can be divided into 3 main components, each requiring a set of commands and manual operations: 1) Brain-Sizer, 2) SABRE, and 3) Lesion-Seg. Brain-Sizer's manual operations involve editing of the automatic skull-stripped total intracranial vault (TIV) extraction mask, designation of ventricular cerebrospinal fluid (vCSF), and removal of subtentorial structures. The SABRE component requires checking of image alignment along the anterior and posterior commissure (ACPC) plane, and identification of several anatomical landmarks required for regional parcellation. Finally, the Lesion-Seg component involves manual checking of the automatic lesion segmentation of subcortical hyperintensities (SH) for false positive errors.
While on-site training of the LE pipeline is preferable, readily available visual teaching tools with interactive training images are a viable alternative. Developed to ensure a high degree of accuracy and reliability, the following is a step-by-step, video-guided, standardized protocol for LE's manual procedures.

Lesion Explorer (LE) is a semi-automatic, image-processing pipeline developed to obtain regional brain tissue and subcortical hyperintensity lesion volumetrics from structural MRI of Alzheimer's disease and normal elderly. To ensure a high level of accuracy and reliability, the following is a video-guided, standardized protocol for LE's manual procedures.

Lesione Explorer: un video-guida, standardizzato protocollo preciso e affidabile Volumetrics MRI-derivati ​​nella malattia di Alzheimer e normale Anziani

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are ...

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As such, primary or &#39;neuronal-like&#39; cell culture systems are commonly utilized. While&#160;these systems are relatively easy to work with, and are useful model systems in which various functional outcomes (such as cell death) can be readily quantified, the examined outcomes and pathways in cultured immature neurons (such as excitotoxicity-mediated cell death pathways) are not necessarily the same as those observed in mature brain, or in intact tissue. Therefore, there is the need to develop models in which cellular mechanisms in mature neural tissue can be examined. We have developed an in vitro technique that can be used to investigate a variety of molecular pathways in intact nervous tissue. The technique described herein utilizes rat cortical tissue, but this technique can be adapted to use tissue from a variety of species (such as mouse, rabbit, guinea pig, and chicken) or brain regions (for example, hippocampus, striatum, etc.). Additionally, a variety of stimulations/treatments can be used (for example, excitotoxic, administration of inhibitors, etc.). In conclusion, the brain slice model described herein can be used to examine a variety of molecular mechanisms involved in excitotoxicity-mediated brain injury.

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

We have developed a brain slice model which can be used to examine molecular mechanisms involved in excitotoxicity-mediated brain injury.&#160;This technique generates viable mature brain tissue and reduces animal numbers required for experimentation, whilst keeping the neuronal circuitry, cellular interactions, and postsynaptic compartments partly intact.

Eccitotossica stimolazione del cervello Microslices come<em&gt; In vitro</em&gt; Modello di Corsa

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As ...

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.

Controllo della Malattia di Parkinson con Adaptive stimolazione cerebrale profonda

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

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases.

Resting-state functional-connectivity MRI has identified abnormalities in patients with a wide range of neuropsychiatric disorders, including epilepsy due to malformations of cortical development. Transcranial Magnetic Stimulation in combination with EEG can demonstrate that patients with epilepsy have cortical hyperexcitability in regions with abnormal connectivity.

Un multimodale Imaging- e stimolazione a base di metodo di valutazione relativi alla connettività del cervello eccitabilità pazienti con epilessia

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations ...

Continuous IV Infusion is the Choice Treatment Route for Arginine-vasopressin Receptor Blocker Conivaptan in Mice to Study Stroke-evoked Brain Edema

Stroke is one of the major causes of morbidity and mortality in the world. Stroke is complicated by brain edema and other pathophysiological events. Among the most important players in the development and evolution of stroke-evoked brain edema is the hormone arginine-vasopressin and its receptors, V1a and V2. Recently, the V1a and V2 receptor blocker conivaptan has been attracting attention as a potential drug to reduce brain edema after stroke. However, animal models which involve conivaptan applications in stroke research need to be modified based on feasible routes of administration. Here the outcomes of 48 hr continuous intravenous (IV) are compared with intraperitoneal (IP) conivaptan treatments after experimental stroke in mice. We developed a protocol in which middle cerebral artery occlusion was combined with catheter installation into the jugular vein for IV treatment of conivaptan (0.2 mg) or vehicle. Different cohorts of animals were treated with 0.2 mg bolus of conivaptan or vehicle IP daily. Experimental stroke-evoked brain edema was evaluated in mice after continuous IV and IP treatments. Comparison of the results revealed that the continuous IV administration of conivaptan alleviates post-ischemic brain edema in mice, unlike the IP administration of conivaptan. We conclude that our model can be used for future studies of conivaptan applications in the context of stroke and brain edema.

Our studies have revealed that the beneficial effects of conivaptan are dependent on the method of delivery after experimental stroke in mice. We have developed a research protocol for delivery of the receptor blocker via IV catheter on stroke-evoked brain edema formation in mice.

Continua infusione endovenosa è la Strada del trattamento scelta per arginina-vasopressina bloccante dei recettori conivaptan nei topi per studiare Stroke-evocato Cervello Edema

Stroke is one of the major causes of morbidity and mortality in the world. Stroke is complicated by brain edema and other pathophysiological events. Among ...

Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans

Neuropathologists, at times, feel intimidated by the amount of knowledge needed to generate definitive diagnoses for complex neuropsychiatric phenomena described in those patients for whom a brain autopsy has been requested. Although the advancements of biomedical sciences and neuroimaging have revolutionized the neuropsychiatric field, they have also generated the misleading idea that brain autopsies have only a confirmatory value. This false idea created a drastic reduction of autopsy rates and, consequently, a reduced possibility to perform more detailed and extensive neuropathological investigations, which are necessary to comprehend numerous normal and pathological aspects yet unknown of the human brain. The traditional inferential method of correlation between observed neuropsychiatric phenomena and corresponding localization/characterization of their possible neurohistological correlates continues to have an undeniable value. In the context of neuropsychiatric diseases, the traditional clinicopathological method is still the best possible methodology (and often the only available) to link unique neuropsychiatric features to their corresponding neuropathological substrates, since it relies specifically upon the direct physical assessment of brain tissues. The assessment of postmortem brains is based on brain cutting procedures that vary across different neuropathology centers. Brain cuttings are performed in a relatively extensive and systematic way based on the various clinical and academic contingencies present in each institution. A more anatomically inclusive and symmetric bi-hemispheric brain cutting methodology should at least be used for research purposes in human neuropathology to coherently investigate, in depth, normal and pathological conditions with the peculiarities of the human brain (i.e., hemispheric specialization and lateralization for specific functions). Such a method would provide a more comprehensive collection of neuropathologically well-characterized brains available for current and future biotechnological and neuroimaging techniques. We describe a symmetric bi-hemispheric brain cutting procedure for the investigation of hemispheric differences in human brain pathologies and for use with current as well as future biomolecular/neuroimaging techniques.

Organized brain cutting procedures are necessary to correlate specific neuropsychiatric phenomena with definitive neuropathologic diagnoses. Brain cuttings are performed differently based on various clinico-academic contingencies. This protocol describes a symmetric bihemispheric brain cutting procedure to investigate hemispheric differences in human brain pathologies and to maximize current and future biomolecular/neuroimaging techniques.

Simmetrica Bihemispheric Postmortem cervello taglio per studiare sano e patologico del cervello Condizioni di esseri umani

Neuropathologists, at times, feel intimidated by the amount of knowledge needed to generate definitive diagnoses for complex neuropsychiatric phenomena ...