この作品は、米陸軍研究局（W911NF-07-1から0415（GS）、W911NF-08-1から0216（GS））とNIH / NIBIB（EB006356（GS）とEB00856でサポートされている補助金によって可能となった（ JRWとGS））。著者らは、関連する技術支援をSigfriedSigProcLAVAモジュールのショーンオースティン、グリフィンMilsapに感謝します。

1。電極のローカリゼーション<ol><li>スライスごとに256×256ピクセル、全視野、補間なし、1mmのスライス幅は、好ましくは、矢状断面：患者の頭部の手術前T1強調MRIの構造を（1.5Tや3T）収集します。 </li><li>グリッドとストリップの外科的移植を観察します。移植グリッド、ストリップの位置にin situでの電極、および神経外科医のノートのデジタル写真を収集します。 </li><li>術後頭蓋骨のX線画像と高分解能で脳のCTスキャン（1 mmのスライス幅は、皮膚への皮膚、ない角度）を収集します。 </li><li>術前MRIを用いて患者の脳の三次元皮質モデルを作成し、ポストグリッド注入CT画像と一緒に共同で登録します。我々は、この目的のためにカレーのソフトウェアパッケージを使用して、MATLAB形式の3D皮質の構造と電極の座標をエクスポートします。 MATLABから、我々は脳にマッピングされた電極を示してムービーを書き出す。我々はまた、Mapは、電極は、自動化されたTalairachアトラスを使用して、標準ブロードエリアに調整します。 </li><li> 3Dモデル、X線画像、写真やメモからの情報を確認してください。電極用のナンバリングスキームを完成させ、電極、これは正確に番号以下のスプリッタボックスにパッチが適用されていることを確認するために、病院の技術で動作します。また、すべての電極の位置が明らかに重複せずに区別することができるように二次元で電極をプロットするための概略レイアウトを作成します。あなたが（セクション4を参照）SIGFRIEDを実行しようとしている場合は、ElectrodeLocationsパラメータで必要とされる形式で、BCI2000パラメータの断片として、これらの2次元座標を保存します。最後に、electrocorticographicallyである可能性が高い二つの電極の位置を選択し、 &quot;サイレント&quot;、すなわち、彼らは（パッチ青いソケットを参照してg.USBampsを準備し、最初のグラウンドとリファレンスとして使用するために、推定された説得力のある皮質の近くではありませんとグランド各ユニットの右端の黄色のソケット）へ。 </li></ol> 2。ハードウェアおよびソフトウェアのセットアップ<ol><li>コンピュータの仕様は、実験の処理要件を処理するために十分であることを確認してください。マルチコアプロセッサは、おそらくリアルタイムデータの収集と処理、ビデオ録画、および他の必要なタスクの要求に対応するために必要となります。 1200 Hzで128チャンネルの録画とリアルタイムの分析のために、我々は、4 GBのRAMで3 GHzのクアッドコアマシンを使用します。アンプは、外部ドライブやカメラなどの他の帯域幅を消費する周辺機器、（これはシステムのデバイスマネージャを経由して検証することができます）で使用されるコントローラ（S）とは異なる専用のUSBコントローラに接続する必要があります。最後に、十分なディスク実験データの1秒あたり5 MBまで保存するためのスペース、およびアーカイブし、それをバックアップするためのシステムがなければなりません。 </li><li>研究機器（アンプ、コンピュータ、実験の画面、keyboを設定すぐに壁にプラグインするだけで、単一の電源コードを使用して、患者の部屋に出入りロールバックすることができ、単一のトロリー、上のARD、スピーカー、マイクとカメラ）。部屋から部屋にコンピュータを移動するには、抜く前に、Hibernateの機能を使用します。患者さんのビデオ画面は、別のトレイテーブルまたはモニターアーム上にある必要があります。患者が発作を起こしやすいことを考えると、医療従事者が患者への即時アクセスを必要とする場合にはすべての機器を迅速にする方法からロールアウトすることができていることを確認してください。装置はまた、患者の部屋の使用前と使用後に消毒ワイプで消毒する必要があります。 </li><li>患者と時間が限られており、すべての手順は、堅牢な、その時間を最大限に活用するために最適化する必要があります。この点で、BCI2000の柔軟性と堅牢性は非常に貴重な特性です。実験は、ボタンのワンタッチで起動できることを確認してください。 BCI2000の場合には、右側の組み合わせを起動するバッチファイルを使用必要なコマンドラインオプションを使用して自動的にBCI2000モジュール。 オペレータとgUSBampSourceモジュールは、特定の実験のために適切なSignalProcessingおよびアプリケーション·モジュールと一緒に、必要とされています。必要なすべてのパラメータ·ファイルがこのような電極とそれらの名前と位置の数として、この患者に固有の任意の、自動的に含めて読み込まれていることを確認しBCI2000のオペレータのスクリプト機能を使用します。この自動化の目的は、実験者による手動ステップ数、したがって、エラーの機会を最小限に抑えることです。ソフトウェアとそのパラメータは、少なくとも1〜2週間注入する前に（おそらくEEG件名）完成し、テストされている必要があります。それはまた、 &quot;ドライ&quot;は、すべての新しい患者固有のパラメータを含む、最初の実験セッションの前日を実行して行うことを強くお勧めします。 </li></ol> 3。実験的なセッションのセットアップ<ol><li>のためにあなたの瞬間を選択してくださいそれらを与えて、患者に実験的なレコーディングを示唆している以前の日に注意して、もう一度あなたが開始15分前。訪問、食事、昼寝、医療処置、患者の肉体的、感情的、認知状態を回避する。それは録音のタイミングと期間を最適化するために、床の上に医療関係者との信頼関係を確立することが重要である。 </li><li>所定の位置に車輪装置は、電源コンセントに接続し、対象者のビデオ画面をオンにし、それをコンピュータに接続し、コンピュータを非冬眠する。 </li><li> BCI2000を起動します。 VisualizeSourceパラメータを有効にすると、 構成の設定を押します。信号のビューアでは、皮質の信号品質を評価させる、開きます。ビューア上で右クリックし、5 Hzのカットオフにハイパスフィルタを設定します。 （このフィルタ設定は、データの収集を視覚化に影響し、されません。） </li><li>電源ラインのノイズからの干渉の確認：（50 Hzまたは60 Hzで、ビューアにノッチフィルタをアクティブにするかあなたがしているどの国によって異なります）信号に大きな違いを生む？その場合、未使用のクロス話しケーブルを取り外す、または電源その他の干渉源を特定し、除去することによって、これを減らすようにしてください。リファレンスとグラウンドの必要に応じて使用される電極を変更します。 </li><li>あなたが目トラッカーを使用している場合は、製造元から提供されているキャリブレーションソフトウェアを使用してキャリブレーションを行ってください。 BCI2000ソースモジュールが含まEyetrackerLogger拡張子付きでコンパイルされるべきであり、使用して起動する必要があります - LogEyetracker = 1フラグがアイトラッキングデータはECOGの信号と同期して取得することができますので、有効になっています。 </li><li>気晴らしや中断を避けるために、可能な信号の干渉を最小限に抑えるために、テレビ、ラジオ、携帯電話の電源がオフになっていることを確認します。 </li><li>あなたが実行しようとしています実験のた​​めに患者に正確な指示を与える。タスクを表示するPowerPointのスライドを用意し、被験者のタスクに応じて、提案した姿勢など、便利な証明することができます。 </lI&gt; <li>実験を開始するにはオペレータの[開始]を押します。 [ スタート]を押すか、または再開するたびに、新しいファイルが以前のデータを上書きしないように作成され、ファイルはすべてのパラメータ値のコピーで初期化されます。あなたがサスペンドキーを押すまでして、イベントマーカとともに、ファイルに自動的にストリーミングされる生データや実験的な実行が完了します。 </li><li>セッションを通して、患者の行動と疑われる発作のECOGの信号を監視し、医療スタッフからの指示に応答する準備ができている。 </li></ol> 4。例の実験セッション：BCI2000とSIGFRIED臨床マッピング<ol><li>準備：セッションが開始する前に、SIGFRIEDモデルを構築するために使用される信号処理の設定が含まれていmodel.iniファイルを準備しておく必要があります、とPRMファイル（または別のPRMの断片。）がBCI2000パラメータを含む。 SigfriedSigProcモジュールリアルタイム可視化のために使用されます。二つの重要なパラメータでは、さまざまなタスクがどのような条件下でマップされますを指定し、この患者の特定の電極と、ElectrodeConditionのために選択した2-Dレイアウトを指定して、ElectrodeLocationsです。この例では、患者に指示を通信するためのシンプルなStimulusPresentationモジュールを使用しているので、 刺激のパラメータはまた、我々は実行する予定のタスクに適応する必要があります。 </li><li>ベースラインのステップ：1200Hzでのすべてのグリッドおよびストリップからサ ​​ンプルECOG活動するように設定gUSBampSource、DummySignalProcessingとStimulusPresentationTaskモジュールを起動し、0.1 Hzでハイパスフィルタ。リラックスして目を見開いてじっとしたままに被写体を指示します。静かな環境で快適な照明の下で、ベースラインの活動の6分を記録します。 </li><li>モデリングのステップ：data2model_guiツールを起動し、5 HzのビンFRで特徴を抽出データのすべての500ミリ秒の最大エントロピー法を用いてOM 70から110 Hzです。ガウス混合物を使用して、選択したスペクトル特徴の確率モデルを構築するモデルの構築を押します。 </li><li>マッピングのステップ：gUSBampSource、SigfriedSigProcLAVAとStimulusPresentationTaskモジュールを起動し、確率モデルをロードするためにオペレータ 、皮質のモデル、および2を設定-と3次元電極の座標を。件名を指示した後、マッピングプロセスを開始します。このプロセスでは、被験者は5回のそれぞれで、一度に10秒間、各タスクを実行します。と説得力のある皮質の3次元マップ - 各タスクの実行中に、SIGFRIEDは、継続的に更新2に示すタスク関連皮質の活性を検出します。 2次元マップで、各円の大きさと赤みは、この特定のタスクで、その重要性を表しています。具体的には、各サークルの大きさはガンマBAで全信号の分散の割合に比例タスクによって占められるを購入する。この統計は、決定係数、又はR 2として知られています。それは範囲内にある（0,1）と現在の設定で0.1の値は、一般的に重要と考えることができます。最大のR 2値に円のスケーリングは、スライダーを（ 図1Cを参照） を使用して制御することができます。 3次元マップで、R 2の値ではなくサークルのサイズとは異なる色にマッピングされています。 </li></ol> 5。代表的な結果 図1は、一人の患者の1 SIGFRIEDマッピングセッションから、代表的な結果を示しています。患者は二次性全般化を左頭発症の難治性局在関連てんかんを持っていた28歳の右利き女性であった。 120 electrocorticographic電極は左前頭葉、頭頂葉と側頭葉皮質を介してsubdurally移植した。横方向のX線（パネル）と術中写真（パネルB）を描く40電極、68電極、3ストリップ4の電極のそれぞれに1高密​​度一時的なグリッドと1正面グリッドの構成を示す。記録された発作から、神経科医は、てんかん焦点をローカライズして、説得力のある言語野を温存しながら左側頭葉の外科的切除を行うために必要であると判断した。これは、正常に実行されました：8ヶ月後の切除では患者が発作フリーとして神経学的欠損せずに評価されている。受動的なマッピングの手順では、リスニングタスクの実行中にタスクに関連した変化を対照することによって大脳皮質は、言語機能に関与する識別SIGFRIED。電極の配置が明確になる2次元インタフェース（パネルC）、および3次元解剖学的に正しいインターフェイス（パネルD）：結果は2インターフェイスで発表されました。左から右へと話し言葉対ベースライン（VOICE）を聞いて、パネルのコントラスト、トーン対ベースライン（トーン）に耳を傾け、そして話し言葉VS LISに耳を傾けトーン（言語）にtening。これらの最後は、受容性言語に固有のもので聴覚機能の大まかな画像として含まれています。 VOICE条件の結果は、この患者の受容性言語機能（パネルの黄色の丸のマーク）が破壊ECSがする位置と良い一致を示した。 <img alt="図1" src="/files/ftp_upload/3993/3993fig1.jpg" /> 図1一人の患者からの結果例。パネルは横方向のX線を示しています。黄色の円は、その後electrocortical刺激マッピングによって識別される、受容性言語に関与する電極をマークします。パネルBは、注入時に撮影した写真です。パネルCは、回路図2次元のレイアウトでSIGFRIEDマッピング結果を示しています。各ディスクのサイズと赤みは、ベースラインに相対的なタスク内の各電極の関与の重要性を表しています。パネルDは、同じ統計は三次元の脳モデルの仁徳の色にマップされています患者のMRIから赤。

<ol>
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利害の衝突が宣言されません。

研究のためのECOGのデータを収集することは非常に学際的なチームは、臨床神経学、脳神経外科、基本的な神経科学、コンピュータサイエンスと電気工学の問題を解決するために、臨床医や研究者間の緊密な協力を必要とします。報酬はECOGの信号は、高ガンマ周波数範囲（70-110Hz）の特定の振幅で、非常に貴重であるということです。彼らは、感覚、認知の神経相関に科学的な洞察を提供し、...

<ol><li> 8×16チャネルg.USBampアンプ（ <a href="http://gtec.at" target="_blank">http://gtec.at</a> ） </li><li> 2×64チャネルブレイクアウトボックス（スプリッタ頭ボックス） </li><li>スプリッタから臨床システムへの2×接続ケーブル</li><li>スプリッタから4 g.USBamps〜2×接続ケーブル</li><li> 4 g.USBamps 2×4ウェイ電源アダプタ</li><li> 4 g.USBampsを同期するための2×4双方向同期アダプター</li><li> 4 g.USBampsの2セットを同期させる1つのxのSyncケーブル</li><li> g.USBamp×1ポテンシャルイコライゼーションクランプ+ケーブル</li><li> 18×Touchproofジャンパケーブル</li><li> 2×4ウェイUSB 2.0ハブ</li><li>電源コード</li><li>ラップトップまたはデスクトップコンピュータ（セクション2.1を参照してください） </li><li>上記のすべてのセキュリティで保護された、可動式カート</li><li>患者のためのEyetracker（または普通の液晶モニター） </li><li>患者モニタ用の可動式トレーテーブル</li><li>患者の行動応答のその他の周辺機器（ジョイスティック等） </li><li> BCI2000ソフトウェア</li><li> ℃アーリソフトウェア</li><li> MATLABソフトウェア</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

我々は侵襲的なてんかんの監視を受けているヒトから研究目的electrocorticographic信号を収集するための手法を提案する。我々は、データ収集、信号処理と刺激プレゼンテーションのためBCI2000ソフトウェアプラットフォームを使用する方法を示します。具体的には、SIGFRIED、リアルタイム脳機能マッピングのためのBCI2000ベースのツールを示しています。

神経科学の研究とリアルタイム機能皮質マッピングのためのヒトElectrocorticographic（ECOG）信号を記録

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

recording-human-electrocorticographic-ecog-signals-for

Research

JoVE Journal

Neuroscience

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

25.5K ビュー.  New York State Department of Health. 我々は侵襲的なてんかんの監視を受けているヒトから研究目的electrocorticographic信号を収集するための手法を提案する。我々は、データ収集、信号処理と刺激プレゼンテーションのためBCI2000ソフトウェアプラットフォームを使用する方法を示します。具体的には、SIGFRIED、リアルタイム脳機能マッピングのためのBCI2000ベースのツールを示しています。

ビデオ: 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.

同時MEGおよびEEGとの機能的マッピング

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

神経科学

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.

人間の前頭前野皮質からfMRI信号への行動応答の相関：タスク分析を用いた認知プロセスを調べる

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.

皮質ネットワークの開発で機能的カルシウムイメージング

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.

単一ユニット活動とElectrocorticographic信号を記録するための慢性神経電極の外科的移植

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

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.

同時MEG / EEGおよび解剖学的に制約のある最小ノルム推定値を使用してマッピング皮質ダイナミクス：聴覚注意の例

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.

ハイフィールドのfMRIを使って大人の猫における聴覚皮質の機能イメージング

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.

管理のリアルタイム fMRI ニューロフィード バック トレーニングのプロトコル

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.

一般的なセットの全皮質のシェットランドシープドッグ配列の慢性注入

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.

動物におけるリアルタイムfMRI脳マッピング

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

Electrocorticographic Recording of Cerebral Cortex Areas Manipulated Using an Adeno-Associated Virus Targeting Cofilin in Mice

The use of electrocorticographic (ECoG) recordings in rodents is relevant to sleep research and to the study of a wide range of neurological conditions. Adeno-associated viruses (AAVs) are increasingly used to improve understanding of brain circuits and their functions. The AAV-mediated manipulation of specific cell populations and/or of precise molecular components has been tremendously useful to identify new sleep regulatory circuits/molecules and key proteins contributing to the adverse effects of sleep loss. For instance, inhibiting activity of the filamentous actin-severing protein&#160;cofilin&#160;using AAV prevents sleep deprivation-induced memory impairment. Here, a protocol is&#160;described that combines the manipulation of cofilin function in a cerebral cortex area with the recording of ECoG activity to examine whether cortical cofilin modulates the wakefulness and sleep ECoG signals. AAV injection is performed during the same surgical procedure as the implantation of ECoG and electromyographic (EMG) electrodes in adult male and female mice. Mice are anesthetized, and their heads are shaved. After skin cleaning and incision, stereotaxic coordinates of the motor cortex are determined, and the skull is pierced at this location. A cannula prefilled with an AAV expressing cofilinS3D, an inactive form of cofilin, is slowly positioned in the cortical tissue. After AAV infusion, gold-covered screws (ECoG electrodes) are screwed through the skull and cemented to the skull with gold wires inserted in the neck muscles (EMG electrodes). The animals are allowed three weeks to recover and to ensure sufficient expression of cofilinS3D. The infected area and cell type are verified using immunohistochemistry, and the ECoG is analyzed using visual identification of vigilance states and spectral analysis. In summary, this combined methodological approach allows the investigation of the precise contribution of molecular components regulating neuronal morphology and connectivity to the regulation of synchronized cerebral cortex activity during wakefulness and sleep.

This article describes a protocol for the manipulation of molecular targets in the cerebral cortex using adeno-associated viruses and for monitoring the effects of this manipulation during wakefulness and sleep using electrocorticographic recordings.

マウスにおけるコフィリンを標的とするアデノ関連ウイルスを用いて操作した大脳皮質領域の電気コルチコチコ

The use of electrocorticographic (ECoG) recordings in rodents is relevant to sleep research and to the study of a wide range of neurological conditions. ...