Les auteurs tiennent à remercier Matti S. Hämäläinen, Lilla Zöllei et trois relecteurs anonymes pour leurs précieux commentaires. Sources de financement: R00DC010196 (AKCL); T32DC000018 (EDL); T32DC005361 (RKM).

1. Anatomique Acquisition et traitement des données <ol><li> Acquérir une aimantation préparé gradient rapide d&#39;écho (MPRAGE) IRM du sujet. Cela peut prendre 5-10 minutes selon le protocole de numérisation spécifique est utilisé. </li><li> L&#39;acquisition de deux autres fast low-angle shot (FLASH) IRM (angles de bascule = 5 ° et 30 °) si les données EEG sont utilisés pour l&#39;analyse d&#39;imagerie inverse, comme des séquences FLASH offrent un contraste des tissus différents à partir des séquences MPRAGE standard 1. </li><li> Utilisez Freesurfer logiciel (voir le tableau) 2, 3 de reconstruire la surface corticale et de mettre en place individuelle M / EEG espace source dipôle. <ol><li> Cet espace source est contraint à la frontière matière grise / blanche segmentée de l&#39;analyse MPRAGE. Chaque hémisphère contient environ 100.000 sommets potentiels, espacés de ~ 1 mm. Pour l&#39;estimation d&#39;amplitude dipolaire (voir ci-dessous), utilisez un espacement de grille de 7 mm, ce qui donne ~ 3000 dipôles par hémisphère. </li></ol></li><li> Reconstruirela peau, le crâne externe et des surfaces intérieures du crâne à partir des images MPRAGE et FLASH utilisant MNE (voir tableau) et Freesurfer. Utiliser ces surfaces pour générer un modèle à trois couches limites élément (BEM). </li></ol> 2. M / EEG d&#39;acquisition de données <ol><li> Préparer sujet de M / EEG enregistrement. <ol><li> Reportez-vous à Liu et al 4 pour les détails de électrooculogramme et la préparation électrode de référence ainsi que la numérisation des monuments les repères du sujet, bobines indicateur de position de tête (HPI) et les électrodes EEG. </li></ol></li><li> Une fois que l&#39;objet est placé dans le MEG, mesurer la position de la tête en utilisant les bobines de HPI. </li><li> Démarrez l&#39;enregistrement. Début de la présentation de stimuli auditifs et visuels. <ol><li> De nombreux matériels et logiciels sont disponibles pour effectuer la présentation du stimulus (p. ex., Présentation, E-Prime). Nous utilisons une Tucker-Davis Technologies Rż6 pour la présentation du stimulus auditif et déclenchement d&#39;emboutissage, avec Psychtoolbox 5 pour visuelles sprésentation timulus, toutes deux contrôlées par MATLAB. Test des latences auditives et visuelles à l&#39;aide d&#39;un microphone et une photodiode attaché à l&#39;écran, puis s&#39;assurer qu&#39;il n&#39;ya pas de gigue observable (ce qui peut nécessiter la mise au projecteur de présentation à sa résolution native) avant l&#39;expérience permet de garantir l&#39;intégrité de synchronisation. </li></ol></li><li> Sujet répond à des stimuli auditifs et visuels par l&#39;intermédiaire d&#39;une boîte à boutons optique tout en effectuant des tâches comportementales. </li><li> Conservez tous les stimuli, les paramètres expérimentaux et les fichiers de données pour l&#39;analyse hors ligne. </li></ol> 3. M / EEG Co-inscription avec IRM et de traitement des données <ol><li> Utilisation du logiciel sur les EMN, charger des données numériseur et reconstruite sujet du modèle social IRM. Choisissez sites repères pour initier la co-registration processus et procéder à recourir à la procédure d&#39;alignement automatique pour compléter la transformation de coordonnées (Figure 2). </li><li> Pour relier l&#39;emplacement de chaque dipôle dans la source de space à l&#39;emplacement de chaque capteur, combiner les données enregistrées HPI (voir 2.2) pour calculer une solution de l&#39;avant avec le BEM trois couches (voir 1.4) </li><li> Inspectez tous enregistrés M / EEG données et d&#39;identifier les canaux qui n&#39;ont écart exceptionnellement élevé ou qui sont complètement à plat. Définissez ces canaux comme canaux mauvaises. </li><li> Utilisez signal-espace de projection 6 ou d&#39;autres techniques de réduction du bruit (comme la séparation d&#39;espace de signal 7) pour projeter ou séparer les modèles de champ spatial origine de la contamination champ ambiant de l&#39;environnement ou d&#39;autres signaux physiologiques indésirables, tels que ceux liés aux oculaires clignote et artefacts cardiaques (Figure 3). <ol><li> Appliquer l&#39;élimination des artefacts dans le domaine temporel (p. ex., En supprimant les époques contenant des signaux d&#39;amplitude anormalement élevés en raison de dopage d&#39;un canal) et l&#39;élimination des artefacts dans le domaine fréquentiel (p. ex., Bande-cran filtrage à 50 ou 60 Hz fréquence de ligne) pour augmenter encore rapport signal-bruit. </li></ol></li><li> Identifier une période de référence où le sujet n&#39;était pas d&#39;effectuer une tâche (p. ex., 200 ms Délai avant le début de chaque essai). Générer une moyenne de ces époques de base afin d&#39;obtenir une estimation de bruit (également connu sous le nom de matrice de covariance). </li><li> Identifier les époques d&#39;intérêt (par exemple, seulement la collecte époques avec bonnes réponses comportementales.) Et définir les conditions de contrastes expérimentales (par exemple, les époques associée à l&#39;objet ayant tourné leur attention auditive à l&#39;hémichamp opposé à l&#39;origine indicé -. &quot;Switch&quot; état ​​- par rapport à l&#39;objet maintien de l&#39;attention sur l&#39;hémichamp originale - &quot;Hold&quot; condition). Générer une réponse moyenne pour chacun de la condition définie. <ol><li> Ces moyennes peuvent être corrigées de base-ou non en fonction des paramètres expérimentaux (voir 8), les données présentées ici sont la ligne de base corrigée. </li></ol></li><li> Combiner la matrice de covariance (3,5) et la solution calculée avant (3,2) pour obtenir unedistribué corticale contraint l&#39;opérateur inverse minimale norme qui concerne les mesures de capteur de dipôles estimations actuelles de l&#39;espace source. <ol><li> Vous pouvez soit environ limiter ou corriger l&#39;orientation des dipôles à la direction corticale normale 9. </li></ol></li><li> Générer un «film cerveau&quot; de l&#39;estimation distribuée dipôle (c&#39;est à dire., L&#39;estimation courante à chaque emplacement dans l&#39;espace de dipôle de source dans le temps) pour chaque condition expérimentale (figure 4). <ol><li> Selon les caractéristiques temporelles de votre plan expérimental, vous pouvez bin vos données en temps par la moyenne des estimations actuelles utilisant des méthodes non-chevauchement des fenêtres temporelles. </li></ol></li></ol> 4. Inférence statistique basée sur un système de coordonnées de surface à base commune <ol><li> Morph les films &quot;cerveau&quot; pour chaque sujet sur une commune (en moyenne) d&#39;espace cortical basées sur un système de coordonnées surface qui ne aligne de manière optimale individuelle sulcal-gysieurs modèles 3. Cela nous permet de comparer ou de moyenne activité corticale dans toutes les matières. (Figure 5). </li><li> Il ya beaucoup de différentes approches d&#39;inférence statistique. Nous soulignerons ici trois approches possibles. Les approches qui ne sont pas mises en œuvre dans le progiciel peut être écrite avec le logiciel, personnalisée et nos exemples, nous utilisons MATLAB pour effectuer le test non paramétrique spatio-temporelle de clustering test de permutation. En dépit de la forte dimensionnalité (espace x temps x Sujets) de ces données, l&#39;ensemble de ces approches peuvent être réalisées en utilisant du matériel standard moderne ordinateur de bureau en quelques secondes (ROI; 4.3 Approche) à des heures (non-paramétrique de clustering; 4,5). </li><li> Région d&#39;intérêt (ROI) approche <ol><li> Vous pouvez définir le retour sur investissement anatomique (p. ex., Définie par l&#39;algorithme de parcellisation automatique 1) et / ou fonctionnelle (p. ex., En enregistrant une tâche fonctionnelle de localisation, comme un Go / No Go tâche d&#39;identifier la saccade oculomotorégions R). </li><li> Vous pouvez limiter davantage votre analyse à un temps spécifique d&#39;intérêt qui convient à votre paradigme expérimental (p. ex., Une période de temps immédiatement avant et après l&#39;apparition des stimuli sonores). Vous pouvez également utiliser d&#39;autres inférence statistique associée à une analyse chronologique. </li></ol></li><li> L&#39;ensemble du cerveau Bonferroni ou faux-Discovery-Rate (FDR) de correction <ol><li> Employer correction de Bonferroni ou FDR si vous avez besoin du cerveau entier, de tous les temps d&#39;analyse. </li><li> Générer une carte statistique à chaque emplacement dipôle et chaque point à l&#39;aide de tests statistiques appropriés, tels que des t-test ou intra-sujets ANOVA pour les données à peu près normalement distribuée. Par exemple, z-scores de la cartographie des paramètres dynamiques statistique des estimations de sources fixes MNE du dipôle 10 peut être utilisé lorsqu&#39;il est associé à une correction des corrélations dans les estimations (par exemple, le conservateur Greenhouse-Geisser correction). </li><li> Pour Bonferronicorrection, obtenir significatifs espace-temps de points par application d&#39;un seuil à un niveau de signification de 0,05 divisé par le nombre de comparaisons (nombre de dipôles multiplié par le nombre de points dans le temps). Pour une approche moins conservatrice, utilisez FDR p-valeur de correction 11. </li></ol></li><li> Non-paramétrique de regroupement spatio-temporelle <ol><li> Utilisez cette méthode (basée sur une simple extension de 12) pour trouver les régions du grand activation spatiale et temporelle cohérente tout en étant moins conservatrice que la correction de Bonferroni, et moins sujettes à des erreurs statistiques de type I que FDR en contrôlant le taux d&#39;erreur famille-sage . <ol><li> Parce que cette approche utilise permutation ou Monte Carlo techniques de ré-échantillonnage, il ne repose pas sur des hypothèses de normalité des données, et suppose seulement que les étiquettes de condition sont échangeables sous l&#39;hypothèse nulle. Bien qu&#39;il soit plus beaucoup de calculs que les deux approches précédentes, il peut encore être effectué en heures sur uneseule machine en utilisant du matériel moderne ordinateur de bureau. </li></ol></li><li> Générer une carte statistique à chaque emplacement dipôle et chaque point à l&#39;aide des statistiques de test appropriées, comme un t-test. </li><li> Seuil cette carte à un seuil de signification préliminaire, par exemple, p &lt;0,05. </li><li> Cluster ces points putatifs significatives basées sur la proximité spatio-temporelle, par exemple. les points importants à moins de 5 ms et 5 mm de distance géodésique de l&#39;autre sont mis dans le même cluster. Note chaque groupe résultant en utilisant hypervolume ou la signification totale (par ex. Somme de t-scores de points dans le cluster). </li><li> Effectuer un ré-échantillonnage standard de permutation (ou ré-échantillonnage de Monte Carlo pour les grands ensembles de données, par exemple. Certain nombre de sujets N&gt; 10, pour sauver le calcul) test avec une statistique maximale (voir 12 pour des exemples de tests de permutation). En bref, pour un sous-ensemble aléatoire des sujets (choix allant de 0 à N sujets), ré-étiqueter les conditions being comparés avant l&#39;obtention de la carte statistique, effectuez le regroupement sur la nouvelle carte statistique, et obtenir la note maximale de cluster pour que le nouvel étiquetage. Effectuer cette procédure sur de nouveaux relabelings aléatoires jusqu&#39;à 2 N permutations pour obtenir une distribution de la statistique maximale; effectuer tout 2 N relabelings possibles on obtient le test de permutation et en utilisant un sous-ensemble aléatoire de moins de 2 N relabelings donne un Monte Carlo (ou aléatoire ) test de permutation. </li><li> Obtenir la signification d&#39;un groupe donné d&#39;origine (à partir de l&#39;étiquetage d&#39;origine), en déterminant la proportion de temps les dimensions maximales sont de cluster supérieure à celle de la grappe d&#39;origine, par exemple. groupes qui sont plus grandes que 95% des grappes statistiques maximales peut être déclaré significatif. <ol><li> Pour une discussion approfondie sur l&#39;inférence statistique en imagerie MEG source distribué, voir 13. </li></ol></li></ol></li><li> Les fichiers de données qui en résultent peuvent être vi<html> sualized à bien des égards, notamment en utilisant les formats nativement utilisés par le logiciel MNE pour stocker spatio-temporelles des estimations corticales, nommément limes STC. Ceux-ci, aux côtés des étiquettes qui peuvent être produits correspondant aux régions importantes, peuvent être générés en utilisant des boîtes à outils MATLAB multinationales prévues et Python. </li></ol> 5. Les résultats représentatifs La figure 6 montre un ensemble de résultats représentatifs en utilisant le paradigme comportemental montre la figure 4. En utilisant la procédure non paramétrique regroupement spatio-temporel (4,5), la FEF droit est considéré comme significatif lorsque le sujet effectue une tâche réorientation par rapport à une tâche standard (figure 6 gauche). En utilisant l&#39;approche ROI (4,3), l&#39;évolution dans le temps de la FEF droite est indiqué, ainsi que la période de temps que ces deux conditions sont sensiblement différentes. p_upload/4262/4262fig1.jpg &quot;/&gt; Figure 1. Workflow pour générer un &quot;film cerveau» à l&#39;aide corticale-contrainte minimale norme estimations dipôle (cf. figure 1 de Liu et al., 2010). <img alt="Figure 2" src="/files/ftp_upload/4262/4262fig2.jpg" /> Figure 2. MNE logiciels utilisés pour faciliter canaux d&#39;EEG et des lieux HPI co-registration sur un sujet IRM de coordonner l&#39;espace. <img alt="Figure 3" src="/files/ftp_upload/4262/4262fig3.jpg" /> Figure 3. Données MEG avant et après l&#39;utilisation de SSP pour enlever cardiaque (surligné en orange) et des yeux clignote (surligné en bleu-vert) des artefacts et filtrage passe-bas pour supprimer la ligne de fréquence. <a href="http://www.jove.com/files/ftp_upload/4262/4262fig3large.jpg" target="_blank">Cliquez ici pour agrandir la figure</a> . <pclass = &quot;jove_content&quot; fo: keep-together.within pages = &quot;always&quot;&gt; <img alt="Figure 4" src="/files/ftp_upload/4262/4262fig4.jpg" /> Figure 4 Un &quot;film cerveaux» natif sujet d&#39;espace cortical et le moment de la présentation audio-visuelle (avec des stimuli auditifs présentés à 600 ms et d&#39;un stimulus visuel présenté à -600 ms) dans un paradigme expérimental (Remarque:. Ce sera présenté comme un film dans le clip final) <img alt="Figure 5" src="/files/ftp_upload/4262/4262fig5.jpg" /> Figure 5. Comparaison entre un retour sur investissement hypothétique mappé sur un sujet natif espace cortical et après transformé sur un espace commun corticale. <img alt="Figure 6" src="/files/ftp_upload/4262/4262fig6.jpg" /> Figure 6. Représentant spatio-temporelle cluster et évolution temporelle associée à la condition expérimentale deuxtions testé.

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Aucun conflit d&#39;intérêt déclaré.

Afin d&#39;estimer l&#39;activation dipôle sur le cortex des MEG acquis / données EEG, nous avons besoin de résoudre un problème inverse, qui n&#39;a pas de solution unique stable à moins appropriées anatomiquement et physiologiquement contraintes sonores sont appliquées. En utilisant la contrainte anatomique acquis pour les sujets individuels utilisant l&#39;IRM et l&#39;adoption de la norme minimale comme critère d&#39;estimation, nous pouvons arriver à une estimation inverse source de courant qui corticale e...

<table border="1"><tbody><tr><td> Nom du matériel / logiciel </td><td> Société / source </td><td></td><td></td></tr><tr><td> 306-canal Vectorview MEG système </td><td> Eleka-Neuromag Ltd, </td><td></td><td></td></tr><tr><td> 1,5-T scanner IRM Avanto </td><td> Siemens Medical Solutions </td><td></td><td></td></tr><tr><td> Freesurfer </td><td></td><td></td><td> <a href="http://freesurfer.net/" target="_blank">http://freesurfer.net/</a> </td></tr><tr><td> MNE logiciel </td><td></td><td></td><td> <a href="http://www.nmr.mgh.harvard.edu/martinos/userInfo/data/sofMNE.php" target="_blank">http://www.nmr.mgh.harvard.edu/martinos/userInfo/data/sofMNE.php</a> </td></tr><tr><td> Électrodes EEG </td><td> Produits du cerveau, Easycap GmbH </td><td></td><td></td></tr><tr><td> 3Space Fastrak système </td><td> Polhemus </td><td></td><td></td></tr><tr><td> Boîte à boutons optique (CRF-932) </td><td> Current Designs </td><td></td><td></td></tr></tbody></table>

mapping cortical dynamics using simultaneous meg/eeg and anatomically-constrained minimum-norm estimates: an auditory attention example

Magnéto-et électro-encéphalographie (MEG / EEG) sont techniques de neuroimagerie offrant une haute résolution temporelle particulièrement adapté pour enquêter sur les réseaux corticaux impliqués dans la dynamique des tâches perceptives et cognitives, telles que la participation à des sons différents dans un cocktail. De nombreuses études antérieures ont utilisé des données enregistrées au niveau du capteur uniquement, c&#39;est à dire., Les champs magnétiques ou les potentiels électriques enregistrés à l&#39;extérieur et sur ​​le cuir chevelu, et ont généralement porté sur une activité qui prend beaucoup de temps enfermé à la présentation du stimulus. Ce type d&#39;événement lié terrain / analyse du potentiel est particulièrement utile quand il ya seulement un petit nombre de modèles distincts dipolaires qui peut être isolée et identifiée dans l&#39;espace et le temps. Sinon, en utilisant des informations anatomiques, ces modèles de terrain distinctes peuvent être localisés en tant que sources actuelles sur le cortex. Cependant, pour une intervention plus soutenue que ne peut-être temps-verrouillé à un stimulus spécifique (p. ex.,en préparation pour l&#39;écoute de l&#39;un des deux simultanément présentés chiffres énoncés basés sur la fonction auditive indicé) ou peuvent être réparties sur plusieurs emplacements spatiaux inconnus a priori, le recrutement d&#39;un réseau distribué corticale peut pas être pris en considération par l&#39;aide d&#39;un nombre limité de sources focales. Ici, nous décrivons une procédure qui utilise des données d&#39;IRM anatomiques individuelles d&#39;établir une relation entre l&#39;information et l&#39;activation du capteur dipôle sur le cortex grâce à l&#39;utilisation d&#39;un minimum-norm estimations (MNE). Cette approche d&#39;imagerie inverse nous fournit un outil pour l&#39;analyse des sources distribuées. À titre d&#39;illustration, nous allons décrire toutes les procédures à l&#39;aide du logiciel Freesurfer et les entreprises multinationales, à la fois disponibles gratuitement. Nous allons résumer les séquences d&#39;IRM et les étapes d&#39;analyse nécessaires pour produire un modèle direct qui nous permet de relier la forme du champ prévu causés par les dipôles distribués sur le cortex sur les capteurs M / EEG. Next, nous allons passer en revue les processus nécessaires qui nous facilitent en débruitage des données du capteur de contaminants environnementaux et physiologiques. Nous allons ensuite décrire la procédure permettant de combiner et de cartographie MEG / EEG données des capteurs sur l&#39;espace cortical, produisant ainsi une famille de séries chronologiques de l&#39;activation corticale dipôle à la surface du cerveau (ou &quot;films du cerveau») liés à chaque condition expérimentale. Enfin, nous mettrons en évidence quelques techniques statistiques qui nous permettent de tirer toute conclusion scientifique à travers une population de sujets (p. ex., Effectuer l&#39;analyse au niveau du groupe) basée sur un espace de coordonnées corticale commune.

Watch this Scientific Journal Video about Mapping Cortical Dynamics Using Simultaneous MEG/EEG and Anatomically-constrained Minimum-norm Estimates: an Auditory Attention Example at JoVE.com

Mapping Cortical Dynamics Using Simultaneous MEG/EEG and Anatomically-constrained Minimum-norm Estimates: an Auditory Attention Example

Nous utilisons et magnéto-électroencéphalographie (MEG / EEG), combinées avec des informations anatomiques capturée par imagerie par résonance magnétique (IRM), pour cartographier la dynamique du réseau cortical associé à l&#39;attention auditive.

Cartographie dynamique corticales à l&#39;aide MEG / EEG simultanés et anatomique contrainte minimum-norm Budget: un exemple L&#39;attention auditive

Magneto- and electroencephalography (MEG/EEG) are neuroimaging techniques that provide a high temporal resolution particularly suitable to investigate the ...

mapping-cortical-dynamics-using-simultaneous-megeeg-anatomically

Research

JoVE Journal

Neuroscience

14.5K vues.  University of Washington. Nous utilisons et magnéto-électroencéphalographie (MEG / EEG), combinées avec des informations anatomiques capturée par imagerie par résonance magnétique (IRM), pour cartographier la dynamique du réseau cortical associé à l'attention auditive.

Vidéo: Mapping Cortical Dynamics Using Simultaneous MEG/EEG and Anatomically-constrained Minimum-norm Estimates: an Auditory Attention Example

Functional Mapping with Simultaneous MEG and EEG

We use magnetoencephalography (MEG) and electroencephalography (EEG) to locate and determine the temporal evolution in brain areas involved in the processing of simple sensory stimuli. We will use somatosensory stimuli to locate the hand somatosensory areas, auditory stimuli to locate the auditory cortices, visual stimuli in four quadrants of the visual field to locate the early visual areas. These type of experiments are used for functional mapping in epileptic and brain tumor patients to locate eloquent cortices. In basic neuroscience similar experimental protocols are used to study the orchestration of cortical activity. The acquisition protocol includes quality assurance procedures, subject preparation for the combined MEG/EEG study, and acquisition of evoked-response data with somatosensory, auditory, and visual stimuli. We also demonstrate analysis of the data using the equivalent current dipole model and cortically-constrained minimum-norm estimates. Anatomical MRI data are employed in the analysis for visualization and for deriving boundaries of tissue boundaries for forward modeling and cortical location and orientation constraints for the minimum-norm estimates.

We use magnetoencephalography (MEG) and electroencephalography (EEG) to map brain areas involved in the processing of simple sensory stimuli.

Cartographie fonctionnelle avec MEG et EEG simultanée

We use magnetoencephalography (MEG) and electroencephalography (EEG) to locate and determine the temporal evolution in brain areas involved in the ...

Recherche

Neurosciences

Preparation and Culture of Chicken Auditory Brainstem Slices

The chicken auditory brainstem is a well-established model system that has been widely used to study the anatomy and physiology of auditory processing at discreet periods of development 1-4 as well as mechanisms for temporal coding in the central nervous system 5-7.
Here we present a method to prepare chicken auditory brainstem slices that can be used for acute experimental procedures or to culture organotypic slices for long-term experimental manipulations.
The chicken auditory brainstem is composed of nucleus angularis, magnocellularis, laminaris and superior olive. These nuclei are responsible for binaural sound processing and single coronal slice preparations preserve the entire circuitry. Ultimately, organotypic slice cultures can provide the opportunity to manipulate several developmental parameters such as synaptic activity, expression of pre and postsynaptic components, expression of aspects controlling excitability and differential gene expression
This approach can be used to broaden general knowledge about neural circuit development, refinement and maturation.

The chicken auditory brainstem is comprised of nuclei responsible for binaural sound processing. A single coronal slice preparation maintains the entire circuitry while the cultured approach provides a unique preparation to study the development of neuronal structure and auditory function at the molecular, cellular and network levels.

Préparation et de la culture de tranches de poulet auditive du tronc

The chicken auditory brainstem is a well-established model system that has been widely used to study the anatomy and physiology of auditory processing at ...

Recording Human Electrocorticographic (ECoG) Signals for Neuroscientific Research and Real-time Functional Cortical Mapping

Neuroimaging studies of human cognitive, sensory, and motor processes are usually based on noninvasive techniques such as electroencephalography (EEG), magnetoencephalography or functional magnetic-resonance imaging. These techniques have either inherently low temporal or low spatial resolution, and suffer from low signal-to-noise ratio and/or poor high-frequency sensitivity. Thus, they are suboptimal for exploring the short-lived spatio-temporal dynamics of many of the underlying brain processes. In contrast, the invasive technique of electrocorticography (ECoG) provides brain signals that have an exceptionally high signal-to-noise ratio, less susceptibility to artifacts than EEG, and a high spatial and temporal resolution (i.e., &lt;1 cm/&lt;1 millisecond, respectively). ECoG involves measurement of electrical brain signals using electrodes that are implanted subdurally on the surface of the brain. Recent studies have shown that ECoG amplitudes in certain frequency bands carry substantial information about task-related activity, such as motor execution and planning1, auditory processing2 and visual-spatial attention3. Most of this information is captured in the high gamma range (around 70-110 Hz). Thus, gamma activity has been proposed as a robust and general indicator of local cortical function1-5. ECoG can also reveal functional connectivity and resolve finer task-related spatial-temporal dynamics, thereby advancing our understanding of large-scale cortical processes. It has especially proven useful for advancing brain-computer interfacing (BCI) technology for decoding a user's intentions to enhance or improve communication6 and control7. Nevertheless, human ECoG data are often hard to obtain because of the risks and limitations of the invasive procedures involved, and the need to record within the constraints of clinical settings. Still, clinical monitoring to localize epileptic foci offers a unique and valuable opportunity to collect human ECoG data. We describe our methods for collecting recording ECoG, and demonstrate how to use these signals for important real-time applications such as clinical mapping and brain-computer interfacing. Our example uses the BCI2000 software platform8,9 and the SIGFRIED10 method, an application for real-time mapping of brain functions. This procedure yields information that clinicians can subsequently use to guide the complex and laborious process of functional mapping by electrical stimulation.
Prerequisites and Planning:
Patients with drug-resistant partial epilepsy may be candidates for resective surgery of an epileptic focus to minimize the frequency of seizures. Prior to resection, the patients undergo monitoring using subdural electrodes for two purposes: first, to localize the epileptic focus, and second, to identify nearby critical brain areas (i.e., eloquent cortex) where resection could result in long-term functional deficits. To implant electrodes, a craniotomy is performed to open the skull. Then, electrode grids and/or strips are placed on the cortex, usually beneath the dura. A typical grid has a set of 8 x 8 platinum-iridium electrodes of 4 mm diameter (2.3 mm exposed surface) embedded in silicon with an inter-electrode distance of 1cm. A strip typically contains 4 or 6 such electrodes in a single line. The locations for these grids/strips are planned by a team of neurologists and neurosurgeons, and are based on previous EEG monitoring, on a structural MRI of the patient's brain, and on relevant factors of the patient's history. Continuous recording over a period of 5-12 days serves to localize epileptic foci, and electrical stimulation via the implanted electrodes allows clinicians to map eloquent cortex. At the end of the monitoring period, explantation of the electrodes and therapeutic resection are performed together in one procedure.
In addition to its primary clinical purpose, invasive monitoring also provides a unique opportunity to acquire human ECoG data for neuroscientific research. The decision to include a prospective patient in the research is based on the planned location of their electrodes, on the patient's performance scores on neuropsychological assessments, and on their informed consent, which is predicated on their understanding that participation in research is optional and is not related to their treatment. As with all research involving human subjects, the research protocol must be approved by the hospital's institutional review board. The decision to perform individual experimental tasks is made day-by-day, and is contingent on the patient's endurance and willingness to participate. Some or all of the experiments may be prevented by problems with the clinical state of the patient, such as post-operative facial swelling, temporary aphasia, frequent seizures, post-ictal fatigue and confusion, and more general pain or discomfort.
At the Epilepsy Monitoring Unit at Albany Medical Center in Albany, New York, clinical monitoring is implemented around the clock using a 192-channel Nihon-Kohden Neurofax monitoring system. Research recordings are made in collaboration with the Wadsworth Center of the New York State Department of Health in Albany. Signals from the ECoG electrodes are fed simultaneously to the research and the clinical systems via splitter connectors. To ensure that the clinical and research systems do not interfere with each other, the two systems typically use separate grounds. In fact, an epidural strip of electrodes is sometimes implanted to provide a ground for the clinical system. Whether research or clinical recording system, the grounding electrode is chosen to be distant from the predicted epileptic focus and from cortical areas of interest for the research. Our research system consists of eight synchronized 16-channel g.USBamp amplifier/digitizer units (g.tec, Graz, Austria). These were chosen because they are safety-rated and FDA-approved for invasive recordings, they have a very low noise-floor in the high-frequency range in which the signals of interest are found, and they come with an SDK that allows them to be integrated with custom-written research software. In order to capture the high-gamma signal accurately, we acquire signals at 1200Hz sampling rate-considerably higher than that of the typical EEG experiment or that of many clinical monitoring systems. A built-in low-pass filter automatically prevents aliasing of signals higher than the digitizer can capture. The patient's eye gaze is tracked using a monitor with a built-in Tobii T-60 eye-tracking system (Tobii Tech., Stockholm, Sweden). Additional accessories such as joystick, bluetooth Wiimote (Nintendo Co.), data-glove (5th Dimension Technologies), keyboard, microphone, headphones, or video camera are connected depending on the requirements of the particular experiment.
Data collection, stimulus presentation, synchronization with the different input/output accessories, and real-time analysis and visualization are accomplished using our BCI2000 software8,9. BCI2000 is a freely available general-purpose software system for real-time biosignal data acquisition, processing and feedback. It includes an array of pre-built modules that can be flexibly configured for many different purposes, and that can be extended by researchers' own code in C++, MATLAB or Python. BCI2000 consists of four modules that communicate with each other via a network-capable protocol: a Source module that handles the acquisition of brain signals from one of 19 different hardware systems from different manufacturers; a Signal Processing module that extracts relevant ECoG features and translates them into output signals; an Application module that delivers stimuli and feedback to the subject; and the Operator module that provides a graphical interface to the investigator.
A number of different experiments may be conducted with any given patient. The priority of experiments will be determined by the location of the particular patient's electrodes. However, we usually begin our experimentation using the SIGFRIED (SIGnal modeling For Realtime Identification and Event Detection) mapping method, which detects and displays significant task-related activity in real time. The resulting functional map allows us to further tailor subsequent experimental protocols and may also prove as a useful starting point for traditional mapping by electrocortical stimulation (ECS).
Although ECS mapping remains the gold standard for predicting the clinical outcome of resection, the process of ECS mapping is time consuming and also has other problems, such as after-discharges or seizures. Thus, a passive functional mapping technique may prove valuable in providing an initial estimate of the locus of eloquent cortex, which may then be confirmed and refined by ECS. The results from our passive SIGFRIED mapping technique have been shown to exhibit substantial concurrence with the results derived using ECS mapping10.
The protocol described in this paper establishes a general methodology for gathering human ECoG data, before proceeding to illustrate how experiments can be initiated using the BCI2000 software platform. Finally, as a specific example, we describe how to perform passive functional mapping using the BCI2000-based SIGFRIED system.

Recording Human Electrocorticographic ECoG Signals for Neuroscientific Research and Real-time Functional Cortical Mapping

We present a method for collecting electrocorticographic signals for research purposes from humans who are undergoing invasive epilepsy monitoring. We show how to use the BCI2000 software platform for data collection, signal processing and stimulus presentation. Specifically, we demonstrate SIGFRIED, a BCI2000-based tool for real-time functional brain mapping.

Enregistrement de l&#39;homme (Electrocorticographic ECoG) Signaux pour la recherche neuroscientifique et en temps réel la cartographie fonctionnelle corticale

Neuroimaging studies of human cognitive, sensory, and motor processes are usually based on noninvasive techniques such as electroencephalography (EEG), ...

Simultaneous Whole-cell Recordings from Photoreceptors and Second-order Neurons in an Amphibian Retinal Slice Preparation

One of the central tasks in retinal neuroscience is to understand the circuitry of retinal neurons and how those connections are responsible for shaping the signals transmitted to the brain. Photons are detected in the retina by rod and cone photoreceptors, which convert that energy into an electrical signal, transmitting it to other retinal neurons, where it is processed and communicated to central targets in the brain via the optic nerve. Important early insights into retinal circuitry and visual processing came from the histological studies of Cajal1,2 and, later, from electrophysiological recordings of the spiking activity of retinal ganglion cells - the output cells of the retina3,4.
A detailed understanding of visual processing in the retina requires an understanding of the signaling at each step in the pathway from photoreceptor to retinal ganglion cell. However, many retinal cell types are buried deep in the tissue and therefore relatively inaccessible for electrophysiological recording. This limitation can be overcome by working with vertical slices, in which cells residing within each of the retinal layers are clearly visible and accessible for electrophysiological recording.
Here, we describe a method for making vertical sections of retinas from larval tiger salamanders (Ambystoma tigrinum). While this preparation was originally developed for recordings with sharp microelectrodes5,6, we describe a method for dual whole-cell voltage clamp recordings from photoreceptors and second-order horizontal and bipolar cells in which we manipulate the photoreceptor's membrane potential while simultaneously recording post-synaptic responses in horizontal or bipolar cells. The photoreceptors of the tiger salamander are considerably larger than those of mammalian species, making this an ideal preparation in which to undertake this technically challenging experimental approach. These experiments are described with an eye toward probing the signaling properties of the synaptic ribbon - a specialized synaptic structure found in a only a handful of neurons, including rod and cone photoreceptors, that is well suited for maintaining a high rate of tonic neurotransmitter release7,8 - and how it contributes to the unique signaling properties of this first retinal synapse.

We describe the preparation of thin retinal slices from aquatic tiger salamanders (Ambystoma tigrinum) and explain how we use these slices to study synaptic processing in the retina by obtaining dual whole-cell voltage clamp recordings from photoreceptors and second-order horizontal and bipolar cells.

Les enregistrements de cellules entières simultanées de photorécepteurs et les neurones de second ordre dans une préparation de tranches rétine Amphibian

One of the central tasks in retinal neuroscience  is to understand the circuitry of retinal neurons and how those connections are  responsible for shaping ...

Functional Imaging of Auditory Cortex in Adult Cats using High-field fMRI

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal models, including monkeys, ferrets, bats, rodents, and cats. In order to draw suitable parallels between human and animal models of auditory function, it is important to establish a bridge between human functional imaging studies and animal electrophysiological studies. Functional magnetic resonance imaging (fMRI) is an established, minimally invasive method of measuring broad patterns of hemodynamic activity across different regions of the cerebral cortex. This technique is widely used to probe sensory function in the human brain, is a useful tool in linking studies of auditory processing in both humans and animals and has been successfully used to investigate auditory function in monkeys and rodents. The following protocol describes an experimental procedure for investigating auditory function in anesthetized adult cats by measuring stimulus-evoked hemodynamic changes in auditory cortex using fMRI. This method facilitates comparison of the hemodynamic responses across different models of auditory function thus leading to a better understanding of species-independent features of the mammalian auditory cortex.

Functional studies of the auditory system in mammals have traditionally been conducted using spatially-focused techniques such as electrophysiological recordings. The following protocol describes a method of visualizing large-scale patterns of evoked hemodynamic activity in the cat auditory cortex using functional magnetic resonance imaging.

Imagerie fonctionnelle du cortex auditif chez chats adultes à l&#39;aide de haut-champ IRMf

Current knowledge of sensory processing in the mammalian auditory system is mainly derived from electrophysiological studies in a variety of animal ...

Optogenetic Stimulation of the Auditory Nerve

Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted deaf subjects1-6. Nonetheless, sound coding with current CIs has poor frequency and intensity resolution due to broad current spread from each electrode contact activating a large number of SGNs along the tonotopic axis of the cochlea7-9. Optical stimulation is proposed as an alternative to electrical stimulation that promises spatially more confined activation of SGNs and, hence, higher frequency resolution of coding. In recent years, direct infrared illumination of&#160;the cochlea has been used to evoke responses in the auditory nerve10. Nevertheless it requires higher energies than electrical stimulation10,11 and uncertainty remains as to the underlying mechanism12. Here we describe a method based on optogenetics to stimulate SGNs with low intensity blue light, using transgenic mice with neuronal expression of channelrhodopsin 2 (ChR2)13 or virus-mediated expression of the ChR2-variant CatCh14. We used micro-light emitting diodes (&#181;LEDs) and fiber-coupled lasers to stimulate ChR2-expressing SGNs through a small artificial opening (cochleostomy) or the round window. We assayed the responses by scalp recordings of light-evoked potentials (optogenetic auditory brainstem response: oABR) or by microelectrode recordings from the auditory pathway and compared them with acoustic and electrical stimulation.

Cochlear implants (CIs) enable hearing by direct electrical stimulation of the auditory nerve. However, poor frequency and intensity resolution limits the quality of hearing with CIs. Here we describe optogenetic stimulation of the auditory nerve in mice as an alternative strategy for auditory research and developing future CIs.

Stimulation optogenetic du nerf auditif

Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted ...

Touchscreen Sustained Attention Task (SAT) for Rats

Sustained attention is the ability to monitor intermittent and unpredictable events over a prolonged period of time. This attentional process subserves other aspects of cognition and is disrupted in certain neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Thus, it is clinically important to identify mechanisms that impair and improve sustained attention. Such mechanisms are often first discovered using rodent models. Therefore, several behavior procedures for testing aspects of sustained attention have been developed for rodents. One, first described by McGaughy and Sarter (1995), called the sustained attention task (SAT), trains rats to distinguish between signal (i.e., brief light presentation) and non-signal trials. The signals are short and thus require careful attention to be perceived. Attentional demands can be increased further by introducing a distractor (e.g., flashing houselight). We have modified this task for touchscreen operant chambers, which are configured with a touchscreen on one wall that can present stimuli and record responses. Here we detail our protocol for SAT in touchscreen chambers. Additionally, we present standard measures of performance in male and female Sprague-Dawley rats. Comparable performance on this task in both sexes highlights its use for attention studies, especially as more researchers are including female rodents in their experimental design. Moreover, the easy implementation of SAT for the increasingly popular touchscreen chambers increases its utility.

Touchscreen Sustained Attention Task SAT for Rats

Sustained attention, or continuously monitoring situations for intermittent and unpredictable events, is a critical aspect of cognition. Here we detail how to test sustained attention in rats using touchscreen operant chambers. We demonstrate comparable performance in male and female rats, making this task useful for studying attention in both sexes.

Écran tactile Sustained Attention spéciale (Sam) pour les Rats

Sustained attention is the ability to monitor intermittent and unpredictable events over a prolonged period of time. This attentional process subserves ...

Simultaneous Recordings of Cortical Local Field Potentials, Electrocardiogram, Electromyogram, and Breathing Rhythm from a Freely Moving Rat

Monitoring the physiological dynamics of the brain and peripheral tissues is necessary for addressing a number of questions about how the brain controls body functions and internal organ rhythms when animals are exposed to emotional challenges and changes in their living environments. In general experiments, signals from different organs, such as the brain and the heart, are recorded by independent recording systems that require multiple recording devices and different procedures for processing the data files. This study describes a new method that can simultaneously monitor electrical biosignals, including tens of local field potentials in multiple brain regions, electrocardiograms that represent the cardiac rhythm, electromyograms that represent awake/sleep-related muscle contraction, and breathing signals, in a freely moving rat. The recording configuration of this method is based on a conventional micro-drive array for cortical local field potential recordings in which tens of electrodes are accommodated, and the signals obtained from these electrodes are integrated into a single electrical board mounted on the animal's head. Here, this recording system was improved so that signals from the peripheral organs are also transferred to an electrical interface board. In a single surgery, electrodes are first separately implanted into the appropriate body parts and the target brain areas. The open ends of all of these electrodes are then soldered to individual channels of the electrical board above the animal's head so that all of the signals can be integrated into the single electrical board. Connecting this board to a recording device allows for the collection of all of the signals into a single device, which reduces experimental costs and simplifies data processing, because all data can be handled in the same data file. This technique will aid the understanding of the neurophysiological correlates of the associations between central and peripheral organs.

This study introduces a method for the simultaneous recording of local field potentials in the brain, electrocardiograms, electromyograms, and breathing signals of a freely moving rat. This technique, which reduces experimental costs and simplifies data analysis, will contribute to the understanding of the interactions between the brain and peripheral organs.

Enregistrements simultanés des potentiels corticaux champ Local, électrocardiogramme, électromyogramme et respiration rythmique d’un Rat librement mobile

Monitoring the physiological dynamics of the brain and peripheral tissues is necessary for addressing a number of questions about how the brain controls ...

Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines

Multiple sclerosis (MS) is the most common immune-mediated disease of the central nervous system (CNS) and progressively leads to physical disability and death, caused by white matter lesions in the spinal cord and cerebellum, as well as by demyelination in grey matter. Whilst conventional models of experimental allergic encephalomyelitis are suitable for the investigation of the cell-mediated inflammation in the spinal and cerebellar white matter, they fail to address grey matter pathologies. Here, we present the experimental protocol for a novel rat model of cortical demyelination allowing the investigation of the pathological and molecular mechanisms leading to cortical lesions. The demyelination is induced by an immunization with low-dose myelin oligodendrocyte glycoprotein (MOG) in an incomplete Freund&#39;s adjuvant followed by a catheter-mediated intracerebral delivery of pro-inflammatory cytokines. The catheter, moreover, enables multiple rounds of demyelination without causing injection-induced trauma, as well as the intracerebral delivery of potential therapeutic drugs undergoing a preclinical investigation. The method is also ethically favorable as animal pain and distress or disability are controlled and relatively minimal. The expected timeframe for the implementation of the entire protocol is around 8 - 10 weeks.

The protocol presented here allows the reproduction of a widespread grey matter demyelination of both cortical hemispheres in adult male Dark Agouti rats. The method comprises of intracerebral implantation of a catheter, subclinical immunization against myelin oligodendrocyte glycoprotein, and intracerebral injection of a pro-inflammatory cytokine mixture through the implanted catheter.

Modèle de rat de démyélinisation corticale cérébrale généralisée induite par une injection intracérébrale de cytokines pro-inflammatoires

Multiple sclerosis (MS) is the most common immune-mediated disease of the central nervous system (CNS) and progressively leads to physical disability and ...

Statistical Modelling of Cortical Connectivity Using Non-invasive Electroencephalograms

Non-invasive electrophysiological recordings are useful for the evaluation of nervous system function. These techniques are inexpensive, fast, replicable, and less resource-intensive than imaging. Further, the functional data produced have excellent temporal resolution, which is not achievable with structural imaging.
Current applications of electroencephalograms (EEG) are limited by data processing methods. Standard analysis techniques using raw time series data at individual channels are very limited methods of interrogating nervous system activity. More detailed information about cortical function can be achieved by examining relationships between channels and deriving statistical models of how areas are interacting, allowing visualization of connectivity between networks.
This manuscript describes a method for deriving statistical models of cortical network activity by recording EEG in a standard manner, then examining the interelectrode coherence measures to assess relationships between the recorded areas. Higher order interactions can be further examined by assessing the covariance between the coherence pairs, producing high-dimensional &#34;maps&#34; of network interactions. These data constructs can be examined to assess cortical network function and its relationship to pathology in ways not achievable with traditional techniques.
This approach offers greater sensitivity to network level interactions than is achievable with raw time series analysis. It is, however, limited by the complexity of drawing specific mechanistic conclusions about the underlying neural populations and the high volumes of data generated, requiring more advanced statistical techniques for evaluation, including dimensionality reduction and classifier-based approaches.

Standard EEG analysis techniques offer limited insight into nervous system function. Deriving statistical models of cortical connectivity offers far greater ability to investigate underlying network dynamics. Improved functional assessment opens new possibilities for diagnosis, prognostication, and outcome prediction in nervous system diseases.

Modélisation statistique de la connectivité corticale à l'aide d'électroencéphalogrammes non invasifs

Non-invasive electrophysiological recordings are useful for the evaluation of nervous system function. These techniques are inexpensive, fast, replicable, ...