この作品は、EFRI-MC3によってサポートされていました：＃1137237 SVSとJTGに授与

すべてのタスクはクリーブランドクリニック財団の治験審査委員会（IRB）に提出し承認されたプロトコルに従って行った。インフォームドコンセントのプロセスは、すべての研究活動の前に各患者で行った。この例では、発作のために移植ステレオ脳波（SEEG）の電極があった研究基準を満たす被験者が選択される。プロジェクトが対象として議論し、彼らは参加を承諾した。 1。患者登録<ol><li>頭蓋内電極の移植を考慮した難治性てんかんの患者を評価します。患者は侵襲手術のための良い候補である場合には、電極の配置を最適化するために、患者のMRI、PETやMEG発作の病理と一緒に分析します。臨床チームは、すべての評価を行い、何の決定は、研究目的のために行われません。 。 </li><li>研究のために適格な患者を特定subsequentの移植のための評価におよび/除外基準に基づいて承認されたIRBプロトコルごとの患者を確認。 注：選択基準でのオーラを持つ被験者が含まれるように、患者の最善の利益である。オーラの患者は、彼らが発作を持ってしようとしていること、研究者に通知することができます。必要な予防措置をとるために、研究者と患者の時間を与える（臨床スタッフに通知するために発作警報を押し、邪魔にならないようにすべての機器を引っ張る）。しかし、被験者が補充される場合、オーラを持たない患者の入力デバイスは、容易に患者の領域から除去できることを確認し、スタッフは研究機器およびプロトコルが認識される。 </li><li> IRBに従っていずれかの研究活動の前にインフォームドコンセントを取得します。インフォームド·コンセントの間に、参加は完全に任意であり、決して患者の臨床ケアに影響を与えることを強調し、研究を説明する。そこに私多くの場合sの直射患者への利益と参加する意欲が利他的である。 </li><li>常に患者さんの権利とプライバシーの尊重を維持します。自分の情報が匿名や機密のままで患者を思い出させる、彼らはありません結果の下の任意の時点で研究への参加を中止する場合があります。 </li><li>患者看板を持っているし、彼または彼女は理解し、研究に参加することに同意する場合は、インフォームドコンセントとデート。のままのコピーが、レビューする患者が残されている。彼らはどんな質問や懸念は、PIに連絡する患者を奨励すべきである。 </li></ol> 2行動システムセットアップ<ol><li>部屋に機器を持って来る前に、十分な患者の部屋のスペースのほか、必要に応じてコンセント（2）へのアクセスがあることを確認してください。 </li><li>すべての機器との配線がセットを迅速化する準備ができていることを確認してください。行動システムは、FDAが続きの対象とすることができ、ロボットアームを（承認済み含みROLタスク中のカーソル）、ラップトップコンピュータは、行動プログラム、タスク刺激を提示するためのモニタ、および電気生理学的および行動データを格納するためのデータ収集システムを制御する。 注：自分の研究の特定のニーズを満たすために必要な変更を加えます。例えば、患者インターフェースの代わりに、ロボットアームのボタンボックスを使用します。 </li><li>患者が現在のタスクを完了するために適切な方法で配置されていない場合は、腕をリクライニングチェア（または床）に患者を支援する、それらは発作を有するべきである。 注：これは、グループは患者と対話する方法を、何が起こっているかを知らせるために、監視ユニットのすべてのメンバーとなど研究デザイン、設備を議論する良いアイデアであり、その可能性のある潜在的な問題生じる。 </li><li>患者の準備ができたら、部​​屋に行動システムを持参し、行動システムやロボットアームをブートアップを開始します。 </li><li>デジタルイベントマルケを接続します時間に順番に電気生理学的収集システムのDCチャンネルに対する行動コンピューターからR出力は、行動イベントマーカーで記録SEEG信号をロックします。 注：このセンターで臨床収集システムと干渉しない研究目的のために指定された別個の電気生理学的収集システムがある。しかしながら、適切な担当者と協力して臨床収集システムを使用することが可能である。すべての努力は、臨床的買収を混乱させないようにする必要があります。 </li><li>ロボットアームを較正し、それがこのような運動の範囲は、患者にとって快適であることを置きます。別のインタフェース·デバイスを使用する場合は、機器が正常に動作しており、使用の対象とするために快適に位置していることを確認してください。 </li><li>ロボットアームを使用している間、緊急停止ボタンは、行動タスク全体の研究者で簡単にアクセスできますことを確認してください。発作の場合には、緊急停止ボタンである押されて、彼らは自分たちに害を与えないように、機器は、患者から引き離されている。さらに、当社は、発作が発生した場合に、患者からの除去を容易にするためのロボットシステムに付属のベルクロストラップを使用しないでください。 注：この例では、行動リグのパラレルポートは、パラレルポートケーブルを使用して取得システムのデジタル入力ポートに接続されている。そのようなロボットアームのX＆Y位置などの追加のアナログ信号が同時に記録されます。 </li></ol> 3行動タスク<ol><li>インタフェース装置のセットアップリグとキャリブレーションの完了後に患者にタスクを説明してください。 </li><li> 「戦争」の子供のカードゲームに似た行動タスクを使用します。そのカードは、コンピュータのカードよりも大きいかどうかの賭けをするために患者情報を確認して下さい。賭け金の選択は、それらのカードの相対値の患者の認識に基づいている。 Tを簡素化唯一のスーツのカードを使用し、2、4、6、8、10奇数カードにデックを制限することによって、その後の分析のために尋ねる。 </li><li> 350ミリ秒のため、画面上の固定のキューを表示します。患者がタスクを開始するために、固定マークの上にカーソルを保持していることを確認してください。 </li><li>千ミリ秒のための刺激を表示します。患者は伏せて横に、コンピュータのカードと自分のカードを見ることができるようにします。 </li><li>カード消失の後、自分のカードに基づいて、5ドルや20ドルのいずれかを賭けるために患者を求め、2つのオプションが表示ゴー·キュー（&lt;5000ミリ秒）を示している。自分が選んだ賭けの上に、ロ​​ボットアームを使用してカーソルを移動させることで賭けをするために患者情報を確認して下さい。位置に基づいて偏りのないことを確認するために裁判に試験から賭け位置をランダム。 </li><li> （ - 1,250ミリ秒1,000）コンピュータのカードの啓示に続く500ミリ秒の遅延（空白画面） - 賭けが選択された後、250に注目してください。 、裁判が勝利したかどうか、成果（千ミリ秒）を守って失う、または描き、どれだけ勝ったか失われた。 </li><li>彼らは彼らのパフォーマンスに自信を持っていると何の質問がなくなるまで、患者が練習できるようにします。 </li></ol> 4。データ収集<ol><li>患者が準備ができたときに、データを記録し、研究（または臨床）取得システムの設定が適切に選択されていることを確認。 </li><li>録音中に、最小限にバックグラウンドノイズを維持するために部屋の照明やテレビの電源をオフにします。さらに、このような、彼らの足をタップ話したり、自分の足を振っとして行動を控えるように患者に尋ねる。 </li><li>タスクを開始し、作業を行う患者を記録。 30分間のタスクを実行するために対象として下さい。ロボットアームシステムのサンプリングレートは1KHzであり、SEEG記録方式のものは、2キロヘルツである。 注：この期間は、他のパラダイムでは異なる場合があります。 </li></ol> 5。データ解析<ol><li>最初に、その患者のフォーマを確保するために記録されたSEEGデータをデ識別するンは、機密のままであり、彼/彼女のデータが匿名で送信されていること。 </li><li>術後のCTや術前のMRIから電極位置の座標を取得します。 </li><li>行動のタスクからの利益のデジタルタイムスタンプを持つ神経生理学的録音を合わせます。 </li><li>イベント依存の脳活動の調節を分析する信号分析方法を適用する。 注：この研究では、事象関連SEEG信号のパワースペクトル密度（PSD）はChronuxのマルチテーパツールボックス26,27を用いて計算した。各試験のデータは、関連するイベント（時間ゼロ）に対して整列し、計算されたPSDは、基準PSDに対する各周波数ビンに正規化した。 </li></ol>

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著者らは、開示することは競合がない。

彼らは行動のタスクに従事ようにここでは、ヒトでの頭蓋内電気生理学的研究を行うための方法を提示してきた。この方法論とその簡単な順列は、人間の動きや認知を研究するために重要である。本質的に任意の技術に利点と欠点が存在する一方で、頭蓋内電極から記録する他の電気生理学的およびイメージング技術に優る利点を有する。主な利点の二つのより良好な制御および行動タスク?...

てんかんは神経細胞のグループからの過度の放電に起因する慢性再発性の発作によって特徴づけられる、最も一般的な脳疾患の一つです。てんかんは世界中で約50万人が罹患し、てんかんを持つすべての患者の約40％が完全に薬物療法1によって制御することができない難治性てんかん発作を持っている。ローカライズおよび外科的に除去または切断されている - 発作の発生（EZてんかんゾーン）を担当する脳領域があれば手術が発作フリーな状態になることがあります。 EZ、可能な皮質及び皮質下の雄弁な領域との近接性の解剖学的位置を定義するために、非侵襲的なツールの配列を使用することができます。発作記号学の分析、ビデオ·頭皮脳波の記録（発作と発作の記録）、神経心理学的検査、磁図（MEG）とMRI 2。非侵襲的なデータはpreciselするのに不十分である場合には雄弁な皮質及び皮質下領域または多焦点発作の可能性がある場合には、慢性侵襲的モニタリングが3,4必要な場合がありますの早期関与の疑いがあるとき、yは、仮想的なEZの場所を定義します。 複数の奥行き電極が三脳内に配置される硬膜下グリッドおよびストリップ、脳の表面上に配置された電極と、ステレオ·脳波（SEEG）を含んでいてもよいEZの位置および境界を定義するための慢性侵襲的なモニタリングの方法次元的。硬膜下頭蓋内記録は、当初、ペンフィールドと同僚がして、その気脳写びまん性脳萎縮5が開示され、旧左側頭-頭頂骨折患者における硬膜外単一の接触電極を使用し、1939年に報告された。 1980年代の間に複数のパブリケーションが彼らを実証した後に続いて、硬膜下グリッドアレイの使用は、より普及するようになった安全性と有効性6。 SEEG法が開発され、普及し、フランスでジャンTailarachとジャンBancaudによって50年代に、ほとんどの耐火焦点てんかん7-9における侵襲マッピングのための選択の方法として、フランスとイタリアで使用されてきたし。 SEEGの原理は、発作記号学と相関して脳内のその主な原理としててんかん放電の3次元空間 - 時間的組織をとり解剖·エレクトロ·臨床相関関係に基づいています。移植戦略を考慮にてんかん様活動の主な組織と発作の伝播に関与して仮想的なてんかんのネットワークを取る着床前仮説に基づいて、電極配置と、個別化されている。いくつかのヨーロッパや北アメリカの最近の報告によると、SEEGの方法論は、深い皮質と皮質下の構造は、複数の連続していないLOから正確な録音を可能にしますBES、及び二国間の探査は、大きな開頭10-15の必要性を回避しながら。その後、術後のイメージが移植された電極の正確な解剖学的位置を取得するために取られる。その後、モニタリング期間の開始とは、患者が移植された電極から発作および発作活動を記録するために1〜4週間の期間のために病院に留まる。そこには追加された危険がなく、患者は、典型的には日常的なモニタリング期間から歓迎猶予として調査研究を見て、このモニタリング期間は、事象関連SEEG分析を用いて脳機能を研究するための適切な時間である。録音は、頭蓋内電極から獲得するだけでなく、てんかんの患者の改善された評価とケアに不可欠であるが、追加的に行動パラダイムの間に人間の脳の活動を研究するための例外的な機会を提供しています。 いくつかの研究者はすでにから侵襲録音を研究する機会を実現していますてんかん患者。 Hill ら。機能的皮質マッピング16のために患者からelectrocorticographic（ECOG）信号を記録するための方法論について報告した。 ECOG記録は、モータ言語のカップリング17に洞察力を提供してきました。移植された深さの電極を有する患者は、18と動き19の学習、メモリ内の脳の振動を研究するためのナビゲーションタスクを実行しました。深電極の録音はまた、海馬の誘発活動20、デフォルトモードネットワーク21内の神経活動、および感情的な処理22の時間的コースとしてそれ以外の場合は達成不可能な時間分解能でのパラダイムを研究するために使用された。 Hudryらは23に一致する短期嗅覚刺激のために彼らの扁桃体に移植SEEG電極を持っていた側頭葉てんかんの患者を調査した。別のグループは、そのような手の屈曲または健康BRAI手や足の一方的な動きのような単純な四肢の動きを研究している移植さSEEG 24,25とてんかん患者からn個のサイト。 上記の研究は、関連文献の非常に多様なコレクションのごく一部である。学び、人間の脳は、行動タスクおよび頭蓋内の記録の組み合わせを使用して、どのように機能するかを理解するために克服できない可能性が存在する。この目標を達成するための他の方法がありますが、頭蓋内記録は、高い時間および空間分解能だけでなく、より深い構造へのアクセスを含むいくつかの利点を有する。著者らは、行動のタスクの間に頭蓋内電極を有する患者から記録するための一般的な方法論を記述することを目指しています。しかし、いくつかの抑止力や障壁を正常介護を受けている患者で臨床研究を完了することがあります。本研究の限界、交絡効果、意義も特定され、検討されます。

<table><tbody><tr><td>InMotion ARM</td><td>Interactive Motion Technologies</td><td>InMotion Arm</td><td>&lt;a href=&quot;http://interactive-motion.com/inmotion-arm-the-new-standard-of-care/&quot;&gt;http://interactive-motion.com/inmotion-arm-the-new-standard-of-care/&lt;/a&gt;&lt;br/&gt; Equipment our lab used, can use other equipment to collect data</td></tr><tr><td>MATLAB</td><td>Mathworks Inc</td><td>MATLAB</td><td>&lt;a href=&quot;http://www.mathworks.com/&quot;&gt;http://www.mathworks.com/&lt;/a&gt;&lt;br/&gt; Need version r2007b or higher to run Monkeylogic</td></tr><tr><td>Data Acquisition Toolbox</td><td>Mathworks Inc</td><td>Data Acquisition Toolbox</td><td>&lt;a href=&quot;http://www.mathworks.com/products/daq/&quot;&gt;http://www.mathworks.com/products/daq/&lt;/a&gt;&lt;br/&gt; Must have to run Monkeylogic</td></tr><tr><td>Image Processing Toolbox</td><td>Mathworks Inc</td><td>Image Processing Toolbox</td><td>&lt;a href=&quot;http://www.mathworks.com/products/image/&quot;&gt;http://www.mathworks.com/products/image/&lt;/a&gt;&lt;br/&gt; Must have to run Monkeylogic</td></tr><tr><td>Monkeylogic</td><td>Wael Asaad and David Freedman</td><td>Monkeylogic</td><td>&lt;a href=&quot;http://www.brown.edu/Research/monkeylogic/&quot;&gt;http://www.brown.edu/Research/monkeylogic/&lt;/a&gt;&lt;br/&gt; Free download, must have MATLAB to run</td></tr><tr><td>Chronux&amp;nbsp;</td><td>Medametrics, LLC&amp;nbsp;</td><td>Data Processing Toolbox</td><td>&lt;a href=&quot;http://www.chronux.org/&quot;&gt;http://www.chronux.org/&lt;/a&gt;</td></tr><tr><td>Brainstorm</td><td></td><td>MEG/EEG Analysis Application</td><td>&lt;a href=&quot;http://neuroimage.usc.edu/brainstorm/&quot;&gt;http://neuroimage.usc.edu/brainstorm/&lt;/a&gt;</td></tr><tr><td>Laptop</td><td>Dell</td><td>Latitude E5530</td><td>&lt;a href=&quot;http://www.dell.com/us/business/p/latitude-e5530/pd?ST=dell%20latitude%20e5530&amp;amp;dgc=ST&amp;amp;cid=263756&amp;amp;lid=4781504&amp;amp;acd=12309152537461010&quot;&gt;http://www.dell.com/us/business/p/latitude-e5530/pd?ST=dell%20latitude%20e5530&amp;amp;dgc=ST&amp;amp;cid=263756&amp;amp;lid=4781504&amp;amp;acd=12309152537461010&lt;/a&gt;</td></tr><tr><td>NI Card</td><td>National Instruments</td><td>NI USB-6008</td><td>&lt;a href=&quot;http://sine.ni.com/nips/cds/view/p/lang/en/nid/201986&quot;&gt;http://sine.ni.com/nips/cds/view/p/lang/en/nid/201986&lt;/a&gt;&lt;br/&gt; 12-Bit, 10 kS/sec Low-Cost Multifunction DAQ</td></tr></tbody></table>

performing behavioral tasks in subjects with intracranial electrodes

ステレオ脳波（SEEG）電極、硬膜下グリッドや深さ、電極のインプラントを持つ患者は、発作焦点と雄弁分野の局在化のための彼らの脳の異なる領域に移植された電極の多数を持っている。脳の病理学的な領域が発見され、場合によっては切除されるまでは、移植後、患者は病院に残しておく必要があります。行動パラダイム任意の数の行動を導く神経相関を明らかにするために行うことができるので、この時間の間に、これらの患者は、研究コミュニティにユニークな機会を提供しています。被験者は意思決定と報酬エンコーディングを評価するために設計された行動のタスクを実行するようにここでは、頭蓋内インプラントからの脳活動を記録するための手法を提案する。頭蓋内電極からのすべての電気生理学的データは、一度に単一の機能に関与する多くの脳領域の検査は行動に関連するスケーリングを可能にし、行動タスク中に記録されている。さらに、および動物実験とは異なり、ヒト患者は、同じ被験体またはコントロールを実行するための複数のタスクを実行する能力を可能にする、迅速に行動さまざまなタスクを学習することができる。人間の脳機能を理解するためのこの技術の多くの利点にもかかわらず、罹患組織から環境因子、鎮痛効果、時間の制約や内容などこれから説明方法論的な制限もある。この方法は、容易に頭蓋評価を実行する任意の機関によって実施されてもよい。直接行動中に人間の脳機能を調べる機会を提供する。

これらの結果では、第二次のタスクを演奏一つの主題で捕捉辺縁系からSEEGデータの分析を提示する。大脳辺縁系（ 図1） - （150Hzの40）変調私たちは、戦争、タスクのさまざまな側面が重要なγ帯域を呼び起こすことを実証することができます。にかかわらず、タスク有事の、視覚野における、高速なレイテンシーの画面の結果上のオブジェクトのプレゼンテーション（〜200ミリ?...

Watch this Scientific Journal Video about Performing Behavioral Tasks in Subjects with Intracranial Electrodes at JoVE.com

Performing Behavioral Tasks in Subjects with Intracranial Electrodes

頭蓋内電極を移植した患者は、患者が行動のタスクを実行している間、脳の複数の領域からの神経学的データを記録するためのユニークな機会を提供する。ここでは、この患者集団へのアクセス権を持つ他の機関では、再現することができ植え込ま患者から記録する方法を提示する。

頭蓋内電極を有する被験者に行動タスクの実行

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in ...

performing-behavioral-tasks-in-subjects-with-intracranial-electrodes

Research

JoVE Journal

Behavior

11.3K ビュー.  Cleveland Clinic Foundation. 頭蓋内電極を移植した患者は、患者が行動のタスクを実行している間、脳の複数の領域からの神経学的データを記録するためのユニークな機会を提供する。ここでは、この患者集団へのアクセス権を持つ他の機関では、再現することができ植え込ま患者から記録する方法を提示する。 

ビデオ: Performing Behavioral Tasks in Subjects with Intracranial Electrodes

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

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

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

脳深部刺激術を受けた覚醒ヒトにおける術中行動作業

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

医学

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

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

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

認知の評価とヒトにおける感情的な関数の組み合わせ侵襲性皮質下および非侵襲性の面神経生理学レコーディング

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

行動学

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 ...

神経科学

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

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

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

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

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), ...

Investigating the Function of Deep Cortical and Subcortical Structures Using Stereotactic Electroencephalography: Lessons from the Anterior Cingulate Cortex

Stereotactic Electroencephalography (SEEG) is a technique used to localize seizure foci in patients with medically intractable epilepsy. This procedure involves the chronic placement of multiple depth electrodes into regions of the brain typically inaccessible via subdural grid electrode placement. SEEG thus provides a unique opportunity to investigate brain function. In this paper we demonstrate how SEEG can be used to investigate the role of the dorsal anterior cingulate cortex (dACC) in cognitive control. We include a description of the SEEG procedure, demonstrating the surgical placement of the electrodes. We describe the components and process required to record local field potential (LFP) data from consenting subjects while they are engaged in a behavioral task. In the example provided, subjects play a cognitive interference task, and we demonstrate how signals are recorded and analyzed from electrodes in the dorsal anterior cingulate cortex, an area intimately involved in decision-making. We conclude with further suggestions of ways in which this method can be used for investigating human cognitive processes.

Stereotactic Electroencephalography (SEEG) is an operative technique used in epilepsy surgery to help localize seizure foci. It also affords a unique opportunity to investigate brain function. Here we describe how SEEG can be used to investigate cognitive processes in human subjects.

定位脳波を使用して、ディープ皮質の機能と下構造の調査：前帯状皮質からの教訓は、

Stereotactic Electroencephalography (SEEG) is a technique used to localize seizure foci in patients with medically intractable epilepsy. This procedure ...

Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes demonstrate the ability to record action potentials from individual or small groups of neurons. Such recorded signals have successfully been used to allow patients to interface with or control&#160;computers, robotic limbs, and their own limbs. However, previous animal studies have shown that a microelectrode implantation in the brain not only damages the surrounding tissue but can also result in functional deficits. Here, we discuss a series of behavioral tests to quantify potential motor impairments following the implantation of intracortical microelectrodes into the motor cortex of a rat. The methods for open field grid, ladder crossing, and grip strength testing provide valuable information regarding the potential complications resulting from a microelectrode implantation. The results of the behavioral testing are correlated with endpoint histology, providing additional information on the pathological outcomes and impacts of this procedure on the adjacent tissue.

We have shown that a microelectrode implantation in the motor cortex of rats causes immediate and lasting motor deficits. The methods proposed herein outline a microelectrode implantation surgery and three rodent behavioral tasks to elucidate potential changes in the fine or gross motor function due to implantation-caused damage to the motor cortex.

ラット皮質運動野の微小電極注入による機能的障害を評価するためにテスト行動の齧歯動物

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes ...

生物工学

Transcranial Electrical Brain Stimulation in Alert Rodents

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in humans is transcranial direct current stimulation (tDCS). Less frequently, transcranial alternating current stimulation (tACS) or transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range, is used. The increase of noninvasive electrical brain stimulation research in humans, both for experimental and clinical purposes, has yielded an increased need for basic, mechanistic, safety studies in animals. This article describes a model for transcranial electrical brain stimulation (tES) through the intact skull targeting the motor system in alert rodents. The protocol provides step-by-step instructions for the surgical set-up of a permanent epicranial electrode socket combined with an implanted counter electrode on the chest. By placing a stimulation electrode into the epicranial socket, different electrical stimulation types, comparable to tDCS, tACS, and tRNS in humans, can be delivered. Moreover, the practical steps for tES in alert rodents are introduced. The applied current density, stimulation duration, and stimulation type may be chosen depending on the experimental needs. The caveats, advantages, and disadvantages of this set-up are discussed, as well as safety and tolerability aspects.

This protocol describes a surgical set-up for a permanent epicranial electrode socket and an implanted chest electrode in rodents. By placing a second electrode into the socket, different types of transcranial electrical brain stimulation can be delivered to the motor system in alert animals through the intact skull.

警告齧歯動物で経頭蓋脳の電気的刺激

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in ...

Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a closed-loop event-triggered manner. Although many studies are focusing on the possible benefits and side-effects of TES in healthy and pathologic brains, there are still many fundamental open questions regarding the mechanism of action of the stimulation. Therefore, there is a clear need for a robust and reproducible method to test the acute and the chronic effects of TES in rodents. TES can be combined with regular behavioral, electrophysiological, and imaging techniques to investigate neuronal networks in vivo. The implantation of transcranial stimulation electrodes does not impose extra constraints on the experimental design while it offers a versatile, flexible tool to manipulate brain activity. Here we provide a detailed, step-by-step protocol to fabricate and implant transcranial stimulation electrodes to influence brain activity in a temporally constrained manner for months.

This detailed protocol describes transcranial stimulation electrode placement on the temporal bone in order to investigate the short- and long-term effects of transcranial electrical stimulation in freely moving rats.

慢性的な経頭蓋電気刺激およびラットの皮質内の記録

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a ...

Analyzing Neural Activity and Connectivity Using Intracranial EEG Data with SPM Software

Measuring neural activity and connectivity associated with cognitive functions at high spatial and temporal resolutions is an important goal in cognitive neuroscience. Intracranial electroencephalography (EEG) can directly record electrical neural activity and has the unique potential to accomplish this goal. Traditionally, averaging analysis has been applied to analyze intracranial EEG data; however, several new techniques are available for depicting neural activity and intra- and inter-regional connectivity. Here, we introduce two analytical protocols we recently applied to analyze intracranial EEG data using the Statistical Parametric Mapping (SPM) software: time-frequency SPM analysis for neural activity and dynamic causal modeling of induced responses for intra- and inter-regional connectivity. We report our analysis of intracranial EEG data during the observation of faces as representative results. The results revealed that the inferior occipital gyrus (IOG) showed gamma-band activity at very early stages (110 ms) in response to faces, and both the IOG and amygdala showed rapid intra- and inter-regional connectivity using various types of oscillations. These analytical protocols have the potential to identify the neural mechanisms underlying cognitive functions with high spatial and temporal profiles.

We present two analytical protocols that can be used to analyze intracranial electroencephalography data using the Statistical Parametric Mapping (SPM) software: time-frequency statistical parametric mapping analysis for neural activity, and dynamic causal modeling of induced responses for intra- and inter-regional connectivity.

神経活動と Spm と頭蓋内脳波データを使用した接続の分析

Measuring neural activity and connectivity associated with cognitive functions at high spatial and temporal resolutions is an important goal in cognitive ...

脳血流と電場のマッピング:マウスにおける電極配置

Placement of Extracranial Stimulating Electrodes and Measurement of Cerebral Blood Flow and Intracranial Electrical Fields in Anesthetized Mice

The detection of cerebral blood flow (CBF) responses to various forms of neuronal activation is critical for understanding dynamic brain function and variations in the substrate supply to the brain. This paper describes a protocol for measuring CBF responses to transcranial alternating current stimulation (tACS). Dose-response curves are estimated both from the CBF change occurring with tACS (mA) and from the intracranial electric field (mV/mm). We estimate the intracranial electrical field based on the different amplitudes measured by glass microelectrodes within each side of the brain. In this paper, we describe the experimental setup, which involves using either bilateral laser Doppler (LD) probes or laser speckle imaging (LSI) to measure the CBF; as a result, this setup requires anesthesia for the electrode placement and stability. We present a correlation between the CBF response and the current as a function of age, showing a significantly larger response at higher currents (1.5 mA and 2.0 mA) in young control animals (12-14 weeks) compared to older animals (28-32 weeks) (p &lt; 0.005 difference). We also demonstrate a significant CBF response at electrical field strengths &lt;5 mV/mm, which is an important consideration for eventual human studies. These CBF responses are also strongly influenced by the use of anesthesia compared to awake animals, the respiration control (i.e., intubated vs. spontaneous breathing), systemic factors (i.e., CO2), and local conduction within the blood vessels, which is mediated by pericytes and endothelial cells. Likewise, more detailed imaging/recording techniques may limit the field size from the entire brain to only a small region. We describe the use of extracranial electrodes for applying tACS stimulation, including both homemade and commercial electrode designs for rodents, the concurrent measurement of the CBF and intracranial electrical field using bilateral glass DC recording electrodes, and the imaging approaches. We are currently applying these techniques to implement a closed-loop format for augmenting the CBF in animal models of Alzheimer's disease and stroke.

著者スポットライト:アルツハイマー病モデルにおける脳血流を改善するための刺激ベースのアプローチ 

We describe a protocol for assessing dose-response curves for extracranial stimulation in terms of brain electrical field measurements and a relevant biomarker-cerebral blood flow. Since this protocol involves invasive electrode placement into the brain, general anesthesia is needed, with spontaneous breathing preferred rather than controlled respirations.

麻酔マウスにおける頭蓋外刺激電極の配置と脳血流および頭蓋内電界の測定

The detection of cerebral blood flow (CBF) responses to various forms of neuronal activation is critical for understanding dynamic brain function and ...