Questo lavoro è stato reso possibile da borse di studio sostenute dalla US Army Research Office (W911NF-07-1-0415 (GS), W911NF-08-1-0216 (GS)) e il NIH / NIBIB (EB006356 (GS) e EB00856 ( JRW e GS)). Gli autori ringraziano Sean Austin per il modulo SigfriedSigProcLAVA e Griffin Milsap per la relativa assistenza tecnica.

1. Elettrodo localizzazione <ol><li> Raccogliere un pre-operatoria T1-pesata risonanza magnetica strutturale (1.5T e 3T) della testa del paziente: 256 x 256 pixel per fetta, il campo pieno di vista, senza interpolazione, 1 fetta di larghezza mm, preferibilmente sezioni sagittali. </li><li> Osservare l&#39;impianto chirurgico delle griglie e strisce. Raccogliere fotografie digitali degli elettrodi in situ, e le note del neurochirurgo sulle posizioni delle griglie impiantati e strisce. </li><li> Raccogliere i post-operatorie cranio immagini a raggi X e TAC del cervello ad alta risoluzione (1 fetta di larghezza mm, pelle a pelle, nessun angolo). </li><li> Creare un modello tridimensionale corticale del cervello del paziente con il pre-operatorio MRI, e co-registrarlo con le immagini di impianto post-CT griglia. Usiamo il pacchetto CURRY software per questo scopo, ed esportare la struttura 3D corticale e l&#39;elettrodo coordinate in formato MATLAB. Da MATLAB, abbiamo esportare un filmato che mostra gli elettrodi mappati sul cervello. Abbiamo anche Map l&#39;elettrodo coordinate standard, aree di Brodmann che utilizzano un sistema automatizzato Talairach atlante. </li><li> Rivedere le informazioni dal modello 3D, X-ray immagini, fotografie e note. Finalizzare uno schema di numerazione per gli elettrodi e il lavoro con i tecnici ospedalieri per garantire che gli elettrodi sono patchati nella scatole splitter dopo questa numerazione esattamente. Inoltre creare un layout schematico per tracciare gli elettrodi in due dimensioni, in modo che tutte le posizioni degli elettrodi possono essere chiaramente distinti senza sovrapposizioni. Se avete intenzione di eseguire Sigfried (vedi sezione 4), salvare queste coordinate bidimensionali come un frammento BCI2000 parametro, nel formato richiesto dal parametro ElectrodeLocations. Infine, selezionare due posizioni degli elettrodi che possono essere electrocorticographically &quot;silenzioso&quot;, cioè, non sono vicino al presunto corteccia eloquente, da utilizzare come un terreno iniziale e di riferimento (preparare le g.USBamps dalla patch il riferimento alle prese blu, e di terraalle prese giallo, sulla destra di ogni unità). </li></ol> 2. Hardware e Software Setup <ol><li> Assicurarsi che le specifiche del computer sono adeguati per gestire i requisiti di elaborazione dell&#39;esperimento. Un processore multi-core sarà probabilmente necessario per soddisfare le esigenze di real-time di acquisizione ed elaborazione dei dati, registrazione video, e altri compiti necessari. Per la registrazione e analisi in tempo reale di 128 canali a 1200 Hz, si usa a 3 GHz quad-core macchina con 4 GB di RAM. Gli amplificatori deve essere collegato ad un apposito controller USB, distinto dal controller (s) utilizzato da altri bandwidth-hungry periferiche, come ad esempio dischi rigidi esterni e videocamere (questo può essere verificato tramite Gestione periferiche del sistema). Infine, ci deve essere spazio sufficiente per memorizzare fino a 5 MB al secondo di dati sperimentali, e di un sistema per l&#39;archiviazione e il backup. </li><li> Impostare il attrezzature di ricerca (amplificatori, computer, schermo sperimentatore, keyboard, altoparlanti, microfono e telecamera) su un unico carrello, che può essere facilmente arrotolato dentro e fuori della stanza del paziente, con un solo cavo di alimentazione singolo collegare alla presa a muro. Per spostare il computer da una stanza all&#39;altra, utilizzare la funzione Hibernate prima di scollegarlo. Schermo video del paziente deve essere su un tavolino separato o braccio del monitor. Considerando che il paziente è soggetto a crisi epilettiche, assicurarsi che tutta l&#39;attrezzatura può essere rotolato fuori strada rapidamente nel caso in cui il personale medico bisogno di un accesso immediato per il paziente. L&#39;attrezzatura deve essere disinfettata con salviette antisettiche prima e dopo l&#39;uso nella stanza del paziente. </li><li> Ora con il paziente è limitato, e tutte le procedure devono essere robusti e ottimizzato per sfruttare al meglio quel momento. A questo proposito, la flessibilità e robustezza di BCI2000 caratteristiche sono preziose. Assicurarsi che gli esperimenti possono essere lanciato con il semplice tocco di un pulsante. In caso di BCI2000, utilizzare un file batch per lanciare la giusta combinazione diBCI2000 moduli automaticamente, con le necessarie opzioni della riga di comando. L&#39;operatore e moduli gUSBampSource sono tenuti, insieme alla SignalProcessing appropriato e moduli applicativi per l&#39;esperimento particolare. Utilizzare la funzionalità di scripting BCI2000 Operator per garantire che tutti i file dei parametri necessari vengono caricati automaticamente, compresi quelli che sono specifici per questo paziente, come ad esempio il numero di elettrodi e loro nomi e posizioni. Lo scopo di questa automazione è quello di minimizzare il numero di operazioni manuali dallo sperimentatore, e così le possibilità di errore. Il software ed i suoi parametri devono essere terminati e collaudati (forse con un soggetto EEG) almeno una o due settimane prima dell&#39;impianto. E &#39;anche altamente consigliabile eseguire un &quot;secco&quot; eseguito il giorno precedente la prima sessione sperimentale, inclusi tutti i nuovi pazienti parametri specifici. </li></ol> 3. Sessione set-up sperimentale <ol><li> Scegli il tuo momento persuggerendo le registrazioni sperimentali per il paziente, dando loro notare nel corso della giornata, e di nuovo 15 minuti prima di iniziare. Aggirare i visitatori, i pasti, i sonnellini, procedure mediche e fisiche del paziente, stato emotivo e cognitivo. E &#39;importante stabilire un rapporto con il personale medico sul pavimento, per aiutare ad ottimizzare i tempi e la durata delle registrazioni. </li><li> Ruota l&#39;apparecchiatura a posto, collegare alla presa di corrente, accendere schermo video del soggetto e collegarlo al computer, e non-ibernare il computer. </li><li> Avviare BCI2000. Con il parametro VisualizeSource abilitato, premere Set Config. Lo spettatore si apre segnale, consentendo di valutare la qualità del segnale ECoG. Fai clic destro sul visualizzatore e impostare il filtro passa-alto ad un cutoff 5 Hz. (Questa impostazione filtro avrà effetto solo sui visualizzazione, e non la raccolta dei dati.) </li><li> Verificare la presenza di interferenze da disturbi sulla linea elettrica: L&#39;attivazione di un filtro notch nel visualizzatore (a 50 Hz o 60 Hz,a seconda del paese in cui ci si trova) fanno una grande differenza per il segnale? In tal caso, provare a ridurre questo rimuovendo i inutilizzati cross-talking cavi, o l&#39;identificazione e la rimozione di altre fonti di interferenza elettrica. Modificare gli elettrodi utilizzati per la terra di riferimento e, se necessario. </li><li> Se si utilizza un eye-tracker, calibrare usando il software di calibrazione fornito dal produttore. Il BCI2000 modulo sorgente deve essere compilato con l&#39;estensione EyetrackerLogger incluso, e dovrebbe essere lanciato con l&#39;opzione - LogEyetracker = 1 flag abilitato, in modo che eye-tracking dati possono essere acquisiti in sincronia con i segnali ECOG. </li><li> Per evitare distrazioni e interruzioni, e per ridurre al minimo le possibili interferenze di segnale, in modo che TV, radio e telefoni cellulari siano spenti. </li><li> Dare istruzioni precise al paziente per l&#39;esperimento che si sta per eseguire. A seconda del compito del soggetto, preparato diapositive Powerpoint che mostrano l&#39;attività, la postura suggerito, ecc, può rivelarsi utile. </li&gt; <li> Premere Avvio della console per avviare l&#39;esperimento. Ogni volta che si preme iniziare o riprendere, un nuovo file verrà creato per evitare di sovrascrivere i dati precedenti, e il file verrà inizializzato con una copia di tutti i valori dei parametri. I dati grezzi saranno poi trasmessi automaticamente al file, con marker di eventi, finché non si preme di sospensione o di esecuzione delle finiture sperimentali. </li><li> Durante la sessione, monitorare il comportamento del paziente ed i segnali di crisi ECOG sospetti, ed essere pronti a rispondere alle istruzioni da parte del personale medico. </li></ol> 4. Esempio sperimentale Session: Sigfried Mapping clinica con BCI2000 <ol><li> Preparazione: prima dell&#39;inizio della sessione, è necessario aver preparato un file model.ini che contiene le impostazioni di elaborazione del segnale Sigfried userà per costruire un modello, e un PRM file (o separati frammenti di PRM.) Contenente i parametri che BCI2000. il modulo SigfriedSigProcutilizzerà per visualizzazione in tempo reale. Due i principali parametri sono ElectrodeLocations, specificando il 2-D layout scelto per elettrodi particolari di questo paziente, e ElectrodeCondition, che specifica che diversi compiti verranno mappati in quali condizioni. In questo esempio, stiamo utilizzando il modulo semplice StimulusPresentation per comunicare le istruzioni al paziente, in modo che il parametro di stimoli ha anche bisogno di essere adeguati alle attività che si intendono eseguire. </li><li> Passo Baseline: Avviare i moduli gUSBampSource, DummySignalProcessing e StimulusPresentationTask, configurato per l&#39;attività di campionamento ECOG da tutte le griglie e strisce a 1200Hz, passa-alto-filtrato a 0,1 Hz. Istruire il soggetto a rilassarsi e rimanere immobile con gli occhi aperti. Record 6 minuti di attività di base, sotto l&#39;illuminazione confortevole in un ambiente tranquillo. </li><li> Modeling Step: Avviare lo strumento data2model_gui ed estrarre le caratteristiche in 5 contenitori Hz from 70-110 Hz utilizzando il metodo massima entropia per ogni 500 ms di dati. Premere Costruisci modello per costruire un modello probabilistico delle caratteristiche spettrali selezionati utilizzando miscele gaussiani. </li><li> Passo Mapping: Avviare il gUSBampSource, SigfriedSigProcLAVA e moduli StimulusPresentationTask e configurare il Operator per caricare il modello probabilistico, il modello corticale, e il 2 - e 3-dimensionali coordinate elettrodi. Dopo istruire il soggetto, avviare il processo di mappatura. In questo processo, un soggetto si esegue ciascuna operazione per 10 secondi alla volta, su ciascuna delle 5 ripetizioni. Durante ogni compito, Sigfried rileva task-attività connesse ECoG che si presenta in continuo aggiornamento 2 - e 3-dimensionali mappe della corteccia eloquente. Nelle due mappe bidimensionali, la dimensione e il rossore di ogni cerchio rappresenta la sua importanza in questo particolare compito. In particolare, la dimensione di ogni cerchio è proporzionale alla quota parte della varianza segnale totale in ba gammand che si spiega con l&#39;attività. Questa statistica è noto come il coefficiente di determinazione, o R 2. È nell&#39;intervallo (0,1) e nella configurazione attuale un valore di 0,1 può generalmente essere considerato significativo. La scala dei cerchi per massimo R 2 valori possono essere controllate mediante i cursori (vedi figura 1C). Nelle tre mappe tridimensionali, i 2 valori di r sono mappati a diversi colori piuttosto che dimensioni dei cerchi. </li></ol> 5. Risultati rappresentativi La figura 1 mostra i risultati rappresentativi, da una sessione di mapping Sigfried in un paziente. Il paziente era un 28-year-old destri sesso femminile che aveva intrattabile epilessia correlata a localizzazione di sinistra-temporale esordio con generalizzazione secondaria. 120 electrocorticographic elettrodi sono stati impiantati più di sinistra subdurally frontale, parietale e la corteccia temporale. Un laterale x-ray (pannello A) e uno intra-operatoria fotografia (pannello B) raffiguranoconfigurazione di una griglia frontale con 40 elettrodi, uno superiore densità griglia temporale con 68 elettrodi, e tre strisce ciascuno di 4 elettrodi. Dalle crisi registrate, un neurologo localizzato il focolai epilettici e ha stabilito che era necessario per eseguire la resezione chirurgica del lobo temporale sinistro, risparmiando corteccia eloquente linguaggio. Questo è stato eseguito con successo: a 8 mesi post-resezione del paziente è stata valutata come libero da crisi convulsive e senza deficit neurologici. La procedura di mappatura passiva Sigfried corteccia identificato coinvolti nella funzione lingua contrasto attività relative modifiche durante le attività di ascolto. I risultati sono stati presentati in due interfacce: un 2-dimensionale di interfaccia (pannello C), che rende la disposizione degli elettrodi chiara, e 3-dimensionale interfaccia anatomicamente corretta-(pannello D). Da sinistra a destra il contrasto pannelli ascolto ai valori basali vs lingua parlata (voce), ascoltando i toni basali vs (toni), e l&#39;ascolto di lingua parlata vs lissi ascolta i toni (lingua). L&#39;ultimo di questi è incluso come un quadro approssimativo della funzione uditiva che è specifico al linguaggio ricettivo. I risultati della condizione VOICE ha mostrato un buon accordo con le posizioni in cui ECS ha sconvolto funzione ricettiva lingua in questo paziente (contrassegnata come cerchi gialli nel pannello A). <img alt="Figura 1" src="/files/ftp_upload/3993/3993fig1.jpg" /> Figura 1. Risultati esempio da una paziente. Panel A presenta un laterale x-ray. Cerchi gialli segnano gli elettrodi implicati nel linguaggio recettivo, come successivamente individuati dalla mappatura stimolazione electrocortical. Panel B è una fotografia scattata durante l&#39;impianto. Pannello C mostra i risultati della mappatura Sigfried in una schematica schema bidimensionale: la dimensione e arrossamento di ciascun disco rappresenta il significato del coinvolgimento di ciascun elettrodo nel compito, rispetto al basale. Nel pannello D, la stessa statistica viene mappato su un colore tridimensionale Rende cervello modellorosso MRI del paziente.

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	<li>Miller, K. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spectral+Changes+in+Cortical+Surface+Potentials+during+Motor+Movement.">Spectral Changes in Cortical Surface Potentials during Motor Movement.</a> Journal of Neuroscience. 27, 2424-2424 (2007).</li><li>Chang, E. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Categorical+speech+representation+in+human+superior+temporal+gyrus.">Categorical speech representation in human superior temporal gyrus.</a> Nature Neuroscience. 13, 1428-1428 (2010).</li><li>Gunduz, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+correlates+of+visual-spatial+attention+in+electrocorticographic+signals+in+humans.">Neural correlates of visual-spatial attention in electrocorticographic signals in humans.</a> Frontiers in Human Neuroscience. 5, (2011).</li><li>Pei, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spatiotemporal+dynamics+of+electrocorticographic+high+gamma+activity+during+overt+and+covert+word+repetition.">Spatiotemporal dynamics of electrocorticographic high gamma activity during overt and covert word repetition.</a> NeuroImage. 54, 2960 (2010).</li><li>Crone, N. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-frequency+gamma+oscillations+and+human+brain+mapping+with+electrocorticography.">High-frequency gamma oscillations and human brain mapping with electrocorticography.</a> Progress in Brain Research. 159, 275 (2006).</li><li>Brunner, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid+communication+with+a+"P300"+matrix+speller+using+electrocorticographic+signals+(ECoG).">Rapid communication with a "P300" matrix speller using electrocorticographic signals (ECoG).</a> Frontiers in Neuroprosthetics. 5, (2010).</li><li>Leuthardt, E. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+brain-computer+interface+using+electrocorticographic+signals+in+humans.">A brain-computer interface using electrocorticographic signals in humans.</a> Journal of Neural Engineering. 1, (2004).</li><li>Schalk, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=BCI2000:+A+General-Purpose+Brain-Computer+Interface+(BCI)+System.">BCI2000: A General-Purpose Brain-Computer Interface (BCI) System.</a> IEEE Transactions in Biomedical Engineering. 51, 1034 (2004).</li><li>Schalk, G., Mellinger, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> A Practical Guide to Brain-Computer Interfacing with BCI2000. , (2010).</li><li>Brunner, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+practical+procedure+for+real-time+functional+mapping+of+eloquent+cortex+using+electrocorticographic+signals+in+humans.">A practical procedure for real-time functional mapping of eloquent cortex using electrocorticographic signals in humans.</a> Epilepsy and Behavior. 15, 278 (2009).</li></ol>

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La raccolta di dati ECOG per la ricerca richiede una stretta collaborazione tra clinici e ricercatori, con un grande team multi-disciplinare risolvere i problemi nei campi della neurologia clinica, neurochirurgia, neuroscienze di base, informatica e ingegneria elettrica. La ricompensa è che i segnali ECOG, e in particolare ampiezza della gamma ad alta frequenza gamma (70-110Hz), sono di grande valore. Non solo fornire la comprensione scientifica dei correlati neurali di cognitive, sensoriali e motorie elabora 1-4<...

<ol><li> 8 x 16 canali amplificatori g.USBamp ( <a href="http://gtec.at" target="_blank">http://gtec.at</a> ) </li><li> 2 x 64 canali break-out box (splitter capo-box) </li><li> 2 x Cavo di collegamento da splitter al sistema clinica </li><li> 2 x Cavo di collegamento da splitter a quattro g.USBamps </li><li> 2 x quattro vie adattatore di alimentazione per quattro g.USBamps </li><li> 2 x quattro direzioni adattatore sync per sincronizzare quattro g.USBamps </li><li> 1 x Cavo di sincronizzazione per sincronizzare due serie di quattro g.USBamps </li><li> 1 x potenziale equalizzazione morsetto + cavo per g.USBamp </li><li> 18 cavi di collegamento x Touchproof </li><li> 2 x quattro vie USB 2.0 hub </li><li> Ciabatta </li><li> Portatile o desktop computer (vedi sezione 2.1) </li><li> Sicura, carrello mobile per tutto il suddetto </li><li> Eyetracker (ordinaria o LCD monitor) per il paziente </li><li> Vassoio di tavolo mobile per il monitor paziente </li><li> Altre periferiche (joystick etc) per pazienti risposte comportamentali </li><li> BCI2000 software </li><li> CUrry software </li><li> Software MATLAB </li></ol>

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.

Watch this Scientific Journal Video about Recording Human Electrocorticographic ECoG Signals for Neuroscientific Research and Real-time Functional Cortical Mapping at JoVE.com

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

Vi presentiamo un metodo per raccogliere i segnali electrocorticographic a fini di ricerca da esseri umani che sono sottoposti a monitoraggio invasivo epilessia. Mostriamo come utilizzare il BCI2000 piattaforma software per la raccolta dati, elaborazione del segnale e la presentazione dello stimolo. In particolare, abbiamo dimostrato Sigfried, uno strumento basato su BCI2000 in tempo reale la mappatura funzionale del cervello.

Registrazione umani Electrocorticographic (ECOG) Segnali per la ricerca neuroscientifica e in tempo reale la mappatura funzionale corticale

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

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Research

JoVE Journal

Neuroscience

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

25.6K Views.  New York State Department of Health. Vi presentiamo un metodo per raccogliere i segnali electrocorticographic a fini di ricerca da esseri umani che sono sottoposti a monitoraggio invasivo epilessia. Mostriamo come utilizzare il BCI2000 piattaforma software per la raccolta dati, elaborazione del segnale e la presentazione dello stimolo. In particolare, abbiamo dimostrato Sigfried, uno strumento basato su BCI2000 in tempo reale la mappatura funzionale del cervello.

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

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.

Mappatura funzionale con EEG e MEG simultaneo

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

Ricerca

Neuroscienze

Correlating Behavioral Responses to fMRI Signals from Human Prefrontal Cortex: Examining Cognitive Processes Using Task Analysis

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar tasks. Participants' behavior during task performance in an fMRI scanner can then be correlated to the brain activity using the blood-oxygen-level-dependent signal. We measure behavior to be able to sort correct trials, where the subject performed the task correctly and then be able to examine the brain signals related to correct performance. Conversely, if subjects do not perform the task correctly, and these trials are included in the same analysis with the correct trials we would introduce trials that were not only for correct performance. Thus, in many cases these errors can be used themselves to then correlate brain activity to them. We describe two complementary tasks that are used in our lab to examine the brain during suppression of an automatic responses: the stroop1 and anti-saccade tasks. The emotional stroop paradigm instructs participants to either report the superimposed emotional 'word' across the affective faces or the facial 'expressions' of the face stimuli1,2. When the word and the facial expression refer to different emotions, a conflict between what must be said and what is automatically read occurs. The participant has to resolve the conflict between two simultaneously competing processes of word reading and facial expression. Our urge to read out a word leads to strong 'stimulus-response (SR)' associations; hence inhibiting these strong SR's is difficult and participants are prone to making errors. Overcoming this conflict and directing attention away from the face or the word requires the subject to inhibit bottom up processes which typically directs attention to the more salient stimulus. Similarly, in the anti-saccade task3,4,5,6, where an instruction cue is used to direct only attention to a peripheral stimulus location but then the eye movement is made to the mirror opposite position. Yet again we measure behavior by recording the eye movements of participants which allows for the sorting of the behavioral responses into correct and error trials7 which then can be correlated to brain activity. Neuroimaging now allows researchers to measure different behaviors of correct and error trials that are indicative of different cognitive processes and pinpoint the different neural networks involved.

The goal of our research is to correlate behavior to brain activity. Accurate behavioral measures and imaging techniques allow us to elucidate brain-behavior relationships.

Correlare risposte comportamentali alla segnali fMRI di Human corteccia prefrontale: Esame Processi Cognitivi Utilizzando Task Analysis

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar ...

Functional Calcium Imaging in Developing Cortical Networks

A hallmark pattern of activity in developing nervous systems is spontaneous, synchronized network activity. Synchronized activity has been observed in intact spinal cord, brainstem, retina, cortex and dissociated neuronal culture preparations. During periods of spontaneous activity, neurons depolarize to fire single or bursts of action potentials, activating many ion channels. Depolarization activates voltage-gated calcium channels on dendrites and spines that mediate calcium influx. Highly synchronized electrical activity has been measured from local neuronal networks using field electrodes. This technique enables high temporal sampling rates but lower spatial resolution due to integrated read-out of multiple neurons at one electrode. Single cell resolution of neuronal activity is possible using patch-clamp electrophysiology on single neurons to measure firing activity. However, the ability to measure from a network is limited to the number of neurons patched simultaneously, and typically is only one or two neurons. The use of calcium-dependent fluorescent indicator dyes has enabled the measurement of synchronized activity across a network of cells. This technique gives both high spatial resolution and sufficient temporal sampling to record spontaneous activity of the developing network.
A key feature of newly-forming cortical and hippocampal networks during pre- and early postnatal development is spontaneous, synchronized neuronal activity (Katz &amp; Shatz, 1996; Khaziphov &amp; Luhmann, 2006). This correlated network activity is believed to be essential for the generation of functional circuits in the developing nervous system (Spitzer, 2006). In both primate and rodent brain, early electrical and calcium network waves are observed pre- and postnatally in vivo and in vitro (Adelsberger et al., 2005; Garaschuk et al., 2000; Lamblin et al., 1999). These early activity patterns, which are known to control several developmental processes including neuronal differentiation, synaptogenesis and plasticity (Rakic &amp; Komuro, 1995; Spitzer et al., 2004) are of critical importance for the correct development and maturation of the cortical circuitry.
In this JoVE video, we demonstrate the methods used to image spontaneous activity in developing cortical networks. Calcium-sensitive indicators, such as Fura 2-AM ester diffuse across the cell membrane where intracellular esterase activity cleaves the AM esters to leave the cell-impermeant form of indicator dye. The impermeant form of indicator has carboxylic acid groups which are able to then detect and bind calcium ions intracellularly.. The fluorescence of the calcium-sensitive dye is transiently altered upon binding to calcium. Single or multi-photon imaging techniques are used to measure the change in photons being emitted from the dye, and thus indicate an alteration in intracellular calcium. Furthermore, these calcium-dependent indicators can be combined with other fluorescent markers to investigate cell types within the active network.

Spontaneous activity of developing neuronal networks can be measured using AM-ester forms of calcium-sensitive indicator dyes. Changes in intracellular calcium, indicating neuronal activation, are detected as transient changes in indicator fluorescence with one- or two-photon imaging. This protocol can be adapted for a range of developmentally-dependent neuronal networks in vitro.

Calcio Imaging funzionale nello sviluppo di reti corticali

A hallmark pattern of activity in developing nervous systems is spontaneous, synchronized network activity. Synchronized activity has been observed in ...

Surgical Implantation of Chronic Neural Electrodes for Recording Single Unit Activity and Electrocorticographic Signals

The success of long-term electrophysiological recordings often depends on the quality of the implantation surgery. Here we provide useful information for surgeons who are learning the process of implanting electrode systems. We demonstrate the implantation procedure of both a penetrating and a surface electrode. The surgical process is described from start to finish, including detailed descriptions of each step throughout the procedure. It should also be noted that this video guide is focused towards procedures conducted in rodent models and other small animal models. Modifications of the described procedures are feasible for other animal models.

We provide useful information for surgeons who are learning the process of implanting chronic neural recording electrodes. Techniques for both penetrating and surface electrode systems are described in a rodent animal model.

Impianto chirurgico di elettrodi neurali cronici per la registrazione di attività singola unità e segnali Electrocorticographic

The success of long-term electrophysiological recordings often depends on the quality of the implantation surgery.  Here we provide useful information for ...

High-resolution Functional Magnetic Resonance Imaging Methods for Human Midbrain

Functional MRI (fMRI) is a widely used tool for non-invasively measuring correlates of human brain activity. However, its use has mostly been focused upon measuring activity on the surface of cerebral cortex rather than in subcortical regions such as midbrain and brainstem. Subcortical fMRI must overcome two challenges: spatial resolution and physiological noise. Here we describe an optimized set of techniques developed to perform high-resolution fMRI in human SC, a structure on the dorsal surface of the midbrain; the methods can also be used to image other brainstem and subcortical structures.
High-resolution (1.2 mm voxels) fMRI of the SC requires a non-conventional approach. The desired spatial sampling is obtained using a multi-shot (interleaved) spiral acquisition1. Since, T2* of SC tissue is longer than in cortex, a correspondingly longer echo time (TE ~ 40 msec) is used to maximize functional contrast. To cover the full extent of the SC, 8-10 slices are obtained. For each session a structural anatomy with the same slice prescription as the fMRI is also obtained, which is used to align the functional data to a high-resolution reference volume.
In a separate session, for each subject, we create a high-resolution (0.7 mm sampling) reference volume using a T1-weighted sequence that gives good tissue contrast. In the reference volume, the midbrain region is segmented using the ITK-SNAP software application2. This segmentation is used to create a 3D surface representation of the midbrain that is both smooth and accurate3. The surface vertices and normals are used to create a map of depth from the midbrain surface within the tissue4.
Functional data is transformed into the coordinate system of the segmented reference volume. Depth associations of the voxels enable the averaging of fMRI time series data within specified depth ranges to improve signal quality. Data is rendered on the 3D surface for visualization.
In our lab we use this technique for measuring topographic maps of visual stimulation and covert and overt visual attention within the SC1. As an example, we demonstrate the topographic representation of polar angle to visual stimulation in SC.

This article describes techniques to perform high-resolution functional magnetic resonance imaging with 1.2 mm sampling in human midbrain and subcortical structures using a 3T scanner. Use of these techniques to resolve topographic maps of visual stimulation in the human superior colliculus (SC) is given as an example.

Ad alta risoluzione magnetica funzionale per immagini Metodi risonanza per mesencefalo umano

Functional MRI (fMRI) is a widely used tool for non-invasively measuring correlates of human brain activity. However, its use has mostly been focused upon ...

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

Magneto- and electroencephalography (MEG/EEG) are neuroimaging techniques that provide a high temporal resolution particularly suitable to investigate the cortical networks involved in dynamical perceptual and cognitive tasks, such as attending to different sounds in a cocktail party. Many past studies have employed data recorded at the sensor level only, i.e., the magnetic fields or the electric potentials recorded outside and on the scalp, and have usually focused on activity that is time-locked to the stimulus presentation. This type of event-related field / potential analysis is particularly useful when there are only a small number of distinct dipolar patterns that can be isolated and identified in space and time. Alternatively, by utilizing anatomical information, these distinct field patterns can be localized as current sources on the cortex. However, for a more sustained response that may not be time-locked to a specific stimulus (e.g., in preparation for listening to one of the two simultaneously presented spoken digits based on the cued auditory feature) or may be distributed across multiple spatial locations unknown a priori, the recruitment of a distributed cortical network may not be adequately captured by using a limited number of focal sources.
Here, we describe a procedure that employs individual anatomical MRI data to establish a relationship between the sensor information and the dipole activation on the cortex through the use of minimum-norm estimates (MNE). This inverse imaging approach provides us a tool for distributed source analysis. For illustrative purposes, we will describe all procedures using FreeSurfer and MNE software, both freely available. We will summarize the MRI sequences and analysis steps required to produce a forward model that enables us to relate the expected field pattern caused by the dipoles distributed on the cortex onto the M/EEG sensors. Next, we will step through the necessary processes that facilitate us in denoising the sensor data from environmental and physiological contaminants. We will then outline the procedure for combining and mapping MEG/EEG sensor data onto the cortical space, thereby producing a family of time-series of cortical dipole activation on the brain surface (or "brain movies") related to each experimental condition. Finally, we will highlight a few statistical techniques that enable us to make scientific inference across a subject population (i.e., perform group-level analysis) based on a common cortical coordinate space.

We use magneto- and electroencephalography (MEG/EEG), combined with anatomical information captured by magnetic resonance imaging (MRI), to map the dynamics of the cortical network associated with auditory attention.

Mappatura Dynamics corticali tramite MEG / EEG simultanee e anatomica vincolata minima norma-Stime: un esempio Attenzione Auditory

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

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.

Imaging funzionale di Auditory Cortex in gatti adulti utilizzando ad alto campo fMRI

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

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain.

The ability to induce and/or control neural plasticity may be critical in future treatments for neurologic disorders and the recovery from brain injury. In this paper, we present a protocol on the use of neurofeedback training with functional magnetic resonance imaging to modulate human brain function.

Un protocollo per l'amministrazione di Real-Time fMRI Neurofeedback Training

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control ...

Chronic Implantation of Whole-cortical Electrocorticographic Array in the Common Marmoset

Electrocorticography (ECoG) allows the monitoring of electrical field potentials from the cerebral cortex with high spatiotemporal resolution. Recent development of thin, flexible ECoG electrodes has enabled conduction of stable recordings of large-scale cortical activity. We have developed a whole-cortical ECoG array for the common marmoset. The array continuously covers almost the entire lateral surface of cortical hemisphere, from the occipital pole to the temporal and frontal poles, and it captures whole-cortical neural activity in one shot. This protocol describes a chronic implantation procedure of the array in the epidural space of the marmoset brain. Marmosets have two advantages regarding ECoG recordings, one being the homologous organization of anatomical structures in humans and macaques, including frontal, parietal, and temporal complexes. The other advantage is that the marmoset brain is lissencephalic and contains a large number of complexes, which are more difficult to access in macaques with ECoG, that are exposed to the brain surface.These features allow direct access to most cortical areas beneath the surface of the brain. This system provides an opportunity to investigate global cortical information processing with high resolutions at a sub-millisecond order in time and millimeter order in space.

We have developed a whole-cortical electrocorticographic array for the common marmoset that continuously covers almost the entire lateral surface of cortex, from the occipital pole to the temporal and frontal poles. This protocol describes a chronic implantation procedure of the array in the epidural space of the marmoset brain.

Impianto cronico di tutto-corticale Electrocorticographic Array nel Marmoset comune

Electrocorticography (ECoG) allows the monitoring of electrical field potentials from the cerebral cortex with high spatiotemporal resolution. Recent ...

Real-Time fMRI Brain Mapping in Animals

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a real-time fMRI platform to guide experimenters to monitor fMRI responses instantaneously during acquisition, which can be used to modify the physiology of animals to achieve desired hemodynamic responses in animal brains. The real-time fMRI set-up is based on a 14.1T preclinical MRI system, enabling the real-time mapping of dynamic fMRI responses in the primary forepaw somatosensory cortex (FP-S1) of anesthetized rats. Instead of a retrospective analysis to investigate confounding sources leading to the variability of fMRI signals, the real-time fMRI platform provides a more effective scheme to identify dynamic fMRI responses using customized macro-functions and a common neuroimage analysis software in the MRI system. Also, it provides immediate troubleshooting feasibility and a real-time biofeedback stimulation paradigm for brain functional studies in animals.

Animal brain functional mapping can benefit from the real-time functional magnetic resonance imaging (fMRI) experimental set-up. Using the latest software implemented in the animal MRI system, we established a real-time monitoring platform for small animal fMRI.

Mappatura cerebrale fMRI in tempo reale negli animali

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a ...