Supported by the 2014-2015 Neurosurgery Research and Education Foundation (NREF) award and a 2014 Grant-In-Aid Award from Louisiana State University Shreveport School of Medicine (J.A.W.). We thank S. Harold and C.M. Keller for their invaluable technical assistance and teaching.

<ol>
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The authors have no competing financial interests with regards to this methodology.

脳深部刺激の正確なメカニズムは完全には特徴付けされていないが、モーターおよび精神障害の両方のためのDBSの有効性は、電気治療と時間6,22-26にわたる様々な皮質下と皮質の脳領域の機能間の動的相互作用に起因する可能性があります。げっ歯類にメタンフェタミン配信の非偶発的な方法は27,28を十分に記載されているが、これらの方法は、薬物動態及び神経化学的効果27〜29の個別の調査のために最も適切です。オペラントの静注薬物自己投与、薬剤のための動機の要素を組み込むことによって、DBSなどの電気治療は時間をかけて病理学的行動との対話方法の研究に最適です。私たちが説明した手順は、異なる環境での偶発的なメタンフェタミンの使用上の1つの環境でのDBSの効果を調べます。 私たちのIVメタンフェタミン自己administにおける3つの重要なステップがあります配給パラダイム：長いアクセスセッション中に薬物摂取の迅速な取得とエスカレーションの1）の誘導、その後の短いアクセスセッション中に薬物摂取の安定した、高レートの2）保守および薬物服用のフロントローディングパターンの3）開発。費用対効果と心理覚せい剤を使用して、げっ歯類でヘッドキャップの潜在限られた寿命を与え、DBSの効果をテストするために理想的に適して両方である、1回の実験当たり12匹のラット - このパラダイムは10で2〜3週間の時間枠で達成することができます。長いアクセス19,30,31の期間を組み込む他のパラダイムのようなこの手順は、合理的に、物質使用障害のいくつかの側面をシミュレートします。それは、レクリエーション利用19,30対人間の依存性の重要な側面である初期のセッション「薬物ローディング、「で、薬物を取得するために使用し、高いモチベーションの両方の拡大を示しています。 IVのメタンフェタミンへの長いアクセス・エクスポージャーを持っているげっ歯類も認知障害32を実証、薬物療法33、薬物動態34 ​​および神経化学的に明確な回答は短いアクセス暴露とげっ歯類よりも慢性メタンフェタミン使用障害を患っているヒトに類似している35を変更します 。 同様に、私たちの脳深部刺激手順における3つの重要なステップがある：一つまたは二つの「モック」セッションのヘッドテザー接続、を含むDBS環境への1）馴化、2）毎日、商用システムを使用してアクティブな刺激の断続的な配信、 3）薬物設定にDBSの切断とその後の輸送を。このパラダイムは、むしろ従来の連続的なDBSよりもTMSのような非侵襲性の治療の過程を模倣するように設計されています。完全に移植され、一般的な運動障害3のために使用されるもののようなプログラム可能なDBSシステムには、いくつかの前述の理由で精神刺激薬依存に苦しむ患者にわずかに可能になります。 Intermitten高リスク手術やアフターケアを伴わない電気治療戦略をT、TMSのように、よりよいこの患者集団に適合させることができます。私たちが説明した方法は、研究者が開発し、制限された時間枠内での薬物環境の外で配信されながら薬物関連の動作を変更することができ、治療戦略を絞り込むことができます。治療が終わった後、36は数週間のために精神科と薬物関連行動の長期的なプラスの効果を発揮全身薬物療法と組み合わせて、特定の神経生理学的欠損23または後にパターン化された過渡頭蓋電気刺激その蓄積の証拠があります。 初期の優れた手術手技のための激しい薬物使用中に複数の手術部位の継続的なケアのニーズが、この方法の主な制限があります。 IVカテーテルまたはDBS電極のどちらかが非動作および/または感染した場合、ラットを行う必要があり調査を終了します。厳格な無菌技術の下で頸静脈カテーテルおよび頭蓋内電極配置は最高の独立これらの手順を開始する前に、経験豊富な研究者から学習されます。 この手順は、の検査を含むいくつかの変更および将来の研究に適している：1）代替刺激パラメータ（例えば、 -刺激波形、パルス幅、周波数、振幅）、2）他の潜在的な治療の脳の標的（ 例えば 、 -側坐核。オペラントセッションの前に様々な間隔で毎日DBS配信、毎週DBS配信、DBS、買収前DBS）、そして、おそらく最もエキサイティングな、 -コア、内側前頭前皮質、中脳、手綱）、3）異なるDBSの配信パターン（例えば、。 4）短期DBSと選択経路のoptogenetic刺激を模倣し、行動修正36に耐え発揮する薬剤の組み合わせを。

メタンフェタミンが原因シナプスモノアミンの急性増加、特にドーパミンに強く、長時間の幸福感を生み出す精神刺激薬です。メタンフェタミン依存性が世界的に推定25万34人のユーザーと無実績のある治療1,2と流行の健康問題です。メタンフェタミン依存性のための新たな治療戦略を開発するための実質的な必要性があります。脳深部刺激（DBS）はパーキンソン病、ジストニア、及び本態性振戦3を含む特定の疾患に発生する破壊的なニューロンの発火パターンを、正規化するために脳「ペースメーカー」を使用して神経外科処置です。最近のヒトの症例報告は、DBSはまた、アルコールや薬物依存の有効な治療法かもしれないが、精神刺激薬に関する前臨床証拠が（ 例えば 、コカイン、メタンフェタミン）は4-8を制限されていることを示唆しています。 それはcurrentlであるように、連続的な脳深部刺激yは、練習患者および彼/彼女の家族からの例外的な協力が必要です。細心の創傷ケアおよび個人衛生があっても、得られた菌血症と静脈内の薬を使用していない患者では、感染を受けやすい基盤となるペースメーカーのハードウェアを保護するために必要とされています。 DBS装置の定期的なフォローアップは、システムの開ループ設計所与も必要です。経験豊富な医師は、日常診療の予定3中にターゲット症状を減少させるために近代的なDBSの設定を変更します。この治療パラダイムは、その挑戦的な心理社会的状況に起因するコカインやメタンフェタミンのユーザーに制限されます。いくつかのげっ歯類の研究では、治療は、薬物使用環境9-11でコカイン自己投与手順の間に連続的に送達されたときに、DBSの効果を調べることによって、この非現実的なパラダイムを模倣しています。 経頭蓋のように、留置ハードウェアを必要としない不連続な技術の非侵襲的磁気刺激（TMS）は、物質使用障害12の治療のためのより良い選択肢かもしれません。 TMSは、毎日、断続的な治療中に特定の脳のターゲット内の電界を発生させるために外部headcoilを用いた非侵襲的に配信されます。 Hコイルまたは「深い」TMSの最近の出現は、その潜在的な使用13,14を拡大し 、皮質のサイトに加えて、より深い脳の構造が刺激されることを可能にします。どちらの治療法は、一次薬物使用とは異なる環境での一連のセッションの間に不連続に配信され、薬物依存13,15-17のためのヒトおよびげっ歯類試験で有望であることを示しています。彼らは暴力や不安定な動作18を体験することができたときにメタンフェタミン依存症患者を治療するためのウィンドウは、おそらくストリート過食中ではない、そのような裁判所の指示によるリハビリなど飲酒の期間中になります。このように、この記事の目的は、一時的であり、電気刺激の送達を記載することです空間的により密接IVのメタンフェタミン依存の治療のために、ヒトにおいて可能であるものを近似する薬剤の使用環境から分離します。

<table>
	<tbody>
		<tr>
			<td>Rodent operant chambers</td>
			<td>Med Associates, Inc</td>
			<td>ENV-008CT</td>
			<td>Med Associates Inc. PO Box 319 St. Albans, Vermont 05478 USA Phone: (802) 527-2343</td>
		</tr>
		<tr>
			<td>Kopf Small Animal Stereotaxic Instrument with Digital Display Console</td>
			<td>Kopf Instruments</td>
			<td>Model 940</td>
			<td>Kopf Phone: 1-877-352-3275 Fax: 1-818-352-3275 Email: sales@kopfinstruments.net</td>
		</tr>
		<tr>
			<td>Z-Series 3-DSP Bioamp Processor</td>
			<td>Tucker Davis Technologies</td>
			<td>RZ5D</td>
			<td>Tucker-Davis Technologies&#160;11930 Research Circle Alachua, FL 32615&#160;USA Ph: 386-462-9622&#160;www.tdt.com</td>
		</tr>
		<tr>
			<td>Z-Series 32-Channel Stimulator</td>
			<td>Tucker Davis Technologies</td>
			<td>IZ2-32</td>
			<td>Software is accompanied by a manual that discusses how to program experiments using the OpenEx platform, which can be accessed here: http://www.tdt.com/files/manuals/OpenEx_User_Guide.pdf</td>
		</tr>
		<tr>
			<td>48 Volt LI-ION Battery Pack for IZ2 Stimulator</td>
			<td>Tucker Davis Technologies</td>
			<td>LZ48-200</td>
			<td></td>
		</tr>
		<tr>
			<td>32-Channel Splitter Box for PZ5</td>
			<td>Tucker Davis Technologies</td>
			<td>S-BOX_PZ5</td>
			<td></td>
		</tr>
		<tr>
			<td>OpenEx Ext Software Package for Multi-Channel Neural Recording</td>
			<td>Tucker Davis Technologies</td>
			<td>OpenEx</td>
			<td></td>
		</tr>
		<tr>
			<td>Platinum-iridium stimulating electrodes</td>
			<td>Plastics One Inc</td>
			<td>MS303/8-B/SPC ELECT PT 2C TW .005&#34;</td>
			<td>Plastics One Inc P.O.Box 21465, S.W. Roanoke, VA 24018, PH 540-772-7950</td>
		</tr>
		<tr>
			<td>2-channel cables between stimulator and commutator</td>
			<td>Plastics One Inc</td>
			<td>305-441/2 W/ Spring</td>
			<td></td>
		</tr>
		<tr>
			<td>2-channel cables between commutator and electrode pedestal</td>
			<td>Plastics One Inc</td>
			<td>305-305 W/ Spring</td>
			<td></td>
		</tr>
		<tr>
			<td>4-channel commutators</td>
			<td>Plastics One Inc</td>
			<td>SL2+2C and SL2+SC/SB</td>
			<td></td>
		</tr>
	</tbody>
</table>

a general method for evaluating deep brain stimulation effects on intravenous methamphetamine self-administration

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

IVの頸静脈カテーテルおよび頭蓋内のDBS電極の配置に続いて、齧歯類が正常に短い回復期間後に自己投与の静脈メタンフェタミンに訓練することができる。 図3は、ラットはに拡張アクセスの2日後にメタンフェタミン自己投与を獲得し、エスカレートすることを示しています4日目までに、セッションごとに168±12注入の平均を有する薬物。 1）メタンフェタミン毒性および永続的な、長期のアクセスを伴う重度の行動の変化を防止し、2）その応答の比較的安定した速度を確立するために、様々なによって操作することができます：ラットは、2つの理由からオペラント訓練の毎日2時間のスケジュールに移動します治療的介入。 図4第二週以上の短いアクセスセッションあたりの全注入の平均数は75±8であり、一般的に10％未満の日々を変化することを示している。 図5は、そのラットのdevelのを示していますオペアンプの日に比べて、トレーニングの6日目まで吸入の「フロントローディング」のパターンの出現によって示されるように、薬剤を取るために増加した動機1.これが発達すると、効果が大きく、その後のセッションで維持される（データは示していません） 。 図6は 、二国間のDBSは、偽刺激群と比較して、3 5の日にオペラントIVのメタンフェタミン自己投与の著しい減少をもたらした非薬物環境で配信することを示しています。 （ - 8.5、MLは2.4±AP + 1.6、DV）核は、シェルは以下の定位を使用して、薬物完了行動8での既知の関与はブレグマからの相対座標を与えられた目標とした側坐核します。刺激パラメータおよび期間は緩く精神疾患8,20,21の治療のためのDBSと以前公開された経験に基づいていたが、実験者のニーズに応じて調整することができます。エラーバーは、すべての日のREA適度ではありません明確な治療効果にもかかわらず、行動評価に見られる応答の範囲を示す、CH意義。実験あたりのラットの数を増やすと、この自然変動を補うことができます。 11匹の動物は、最初に、この実験に用いました。 （; N = 4アクティブDBS N = 4シャム）ワン動物が手術後に食欲不振のために安楽死させ、1動物が原因で発作を除外した、1動物は、8匹の動物の合計で私たちを残しによるDBS電極の誤動作に除外されました。その正常に完了を可能にする、各実験のために12匹 - 一般的には約10から始まります。 <img alt="図1" src="/files/ftp_upload/53266/53266fig1.jpg" /> 図1. ビジュアルプログラミング言語。研究者は、複数のアニマに脳刺激を提供することができますプログラムを設計するために、ここに示す例のように、視覚的なプログラミング言語を使用していますLS同時に、ユーザーが入力したパラメータで。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig1large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a> <img alt="図2" src="/files/ftp_upload/53266/53266fig2.jpg" /> 図2. ビジュアルコントロールパネル。実験の開始に先立ち、研究者は、ビジュアルコントロールパネルの左側にある所望の周波数、パルス幅、および振幅を指定します。ここで刺激パラメータは以下のとおりです。電流強度200μA。パルス幅61ミリ秒。パルス周波数130ヘルツ。刺激が開始されると、アクティブ電流送達するための波形が右側に表示されている。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig2large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a> IVメタンフェタミン自己管理の 図3. 獲得。合計オペラント応答（360分）のデータを反復測定として定義され、毎日のセッションを反復測定ANOVAを用いて分析しました。 p &lt;0.05であったすべての分析は、有意であるとみなしました。データは平均±標準誤差です。オペラント訓練の最初の4日間毎日6時間のオペラントセッション中総メタンフェタミン注入。+ P &lt;0.05セッション1と2に比べて<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig3large.jpg" target="_blank">、この図の拡大版をご覧になるにはこちらをクリックしてください。</a> <img alt="図4" src="/files/ftp_upload/53266/53266fig4.jpg" /> 図4。IVメタンフェタミン自己管理のメンテナンス。合計オペラント応答（120分）のデータは、反復測定として定義され、毎日のセッションでの反復測定ANOVAを用いて分析しました。 p &lt;0.05であったすべての分析は、有意であるとみなしました。データは平均±標準誤差です。安定したが、強烈な服薬行動を実証オペラント訓練、第2週にわたり毎日2時間のオペラントセッション中総メタンフェタミン注入。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig4large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a> <img alt="図5" src="/files/ftp_upload/53266/53266fig5.jpg" /> 薬を服用するための動機の 図5. 開発応答オペラントは、最初の一時間とデータのための15分毎に繰り返し、私を使用して分析した集計されましたANOVAは、反復測定のように定義された各15分象限でasures。 p &lt;0.05であったすべての分析は、有意であるとみなしました。データは平均±標準誤差です。 「フロントローディング」のパターンがオペラント訓練の1日目には存在しないが、薬を服用する強い意欲を示し、第二週によって開発しています。 + P &lt;0.05は、60分に比べて45〜60分に比べて30、45、および60分、++ P &lt;0.05、+++ P &lt;0.05と比較する。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig5large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a> <img alt="図6" src="/files/ftp_upload/53266/53266fig6.jpg" /> 図6. IVメタンフェタミン自己投与のDBS影響。最初の一時間で応答総オペラントは（60分）のデータがbetweで混合ANOVAを用いて分析しました治療の対象変数（シャム対 DBS）、毎日のセッションの反復測定が備わっています。 p &lt;0.05であったすべての分析は、有意であるとみなしました。データは平均±標準誤差です。二国間事前オペラント脳深部刺激が大幅に処置日3、4で応答オペラントの最初の60分間にわたってメタンフェタミン注入の数を減少し、偽群およびベースライン応答に比べ7 + P &lt;0.05。終了毎日の治療後のベースラインレベルに戻った応答。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53266/53266fig6large.jpg" target="_blank">この図の拡大版をご覧になるにはこちらをクリックしてください。</a>

Watch this Scientific Journal Video about A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration at JoVE.com

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

静脈内メタンフェタミン自己管理に脳深部刺激効果を評価するための一般的な方法

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people.  There is a need ...

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15.1K ビュー.  Louisiana State University. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

ビデオ: A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout&#160;or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e.&#160;8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e.&#160;one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.

The current study evaluates a novel procedure for assessing the reinforcing effects of palatable solutions in laboratory rats: intraoral self-administration. To this end, operant responding (i.e.&#160;lever pressing) for intraoral infusions of sweet solutions at different concentrations was measured on continuous and progressive ratios schedules of reinforcement.

実験用ラットにおける味物質の強化特性を評価するための新しい方法：オペラント口腔内自己投与

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste ...

行動学

Transcranial Magnetic Stimulation for Investigating Causal Brain-behavioral Relationships and their Time Course

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily disrupt information processing in a brain region, generating a short-lived &#8220;virtual lesion.&#8221; Stimulation that interferes with task performance indicates that the affected brain region is necessary to perform the task normally. In other words, unlike neuroimaging methods such as functional magnetic resonance imaging (fMRI) that indicate correlations between brain and behavior, TMS can be used to demonstrate causal brain-behavior relations. Furthermore, by varying the duration and onset of the virtual lesion, TMS can also reveal the time course of normal processing. As a result, TMS has become an important tool in cognitive neuroscience. Advantages of the technique over lesion-deficit studies include better spatial-temporal precision of the disruption effect, the ability to use participants as their own control subjects, and the accessibility of participants. Limitations include concurrent auditory and somatosensory stimulation that may influence task performance, limited access to structures more than a few centimeters from the surface of the scalp, and the relatively large space of free parameters that need to be optimized in order for the experiment to work. Experimental designs that give careful consideration to appropriate control conditions help to address these concerns. This article illustrates these issues with TMS results that investigate the spatial and temporal contributions of the left supramarginal gyrus (SMG) to reading.

Transcranial magnetic stimulation (TMS) is a technique for non-invasively disrupting neural information processing and measuring its effect on behavior. When TMS interferes with a task, it indicates that the stimulated brain region is necessary for normal task performance, allowing one to systematically relate brain regions to cognitive functions.

因果脳行動の関係とその経時変化を調査するための経頭蓋磁気刺激

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily ...

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species.
Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Shuttle-box avoidance learning is well-established in behavioral neuroscience. This protocol describes how shuttle-box learning in rodents can be combined with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical in vivo recordings as a tool to study multiple aspects of learning and perception.

知覚と学習を研究するためのツールと​​しての電気生理学的皮質の記録と刺激と組み合わせたシャトル・ボックストレーニング

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the ...

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.

Vagus nerve stimulation (VNS) has emerged as a tool to induce targeted synaptic plasticity in the forebrain to modify a range of behaviors. This protocol describes how to implement VNS to facilitate the consolidation of fear extinction memory.

ツールとしての迷走神経刺激は、絶滅の学習のための関連経路の可塑性を誘導するために

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been ...

A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods require saccharin/sucrose fading, water deprivation and/or extended training to initiate operant responding in rats. This paper describes a novel and efficient method to quickly initiate operant responding for ethanol that is convenient for experimenters and does not require water deprivation or saccharin/sucrose fading, thus eliminating the potential confound of using sweeteners in ethanol operant self-administration studies. With this method, Wistar rats typically acquire and maintain self-administration of a 20% ethanol solution in less than two weeks of training. Furthermore, blood ethanol concentrations and rewards are positively correlated for a 30 min self-administration session. Moreover, naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress ethanol self-administration in rodents, dose-dependently decreases alcohol intake and motivation to consume alcohol for rats self-administering 20% ethanol, thus validating the use of this new method to study the reinforcing properties of alcohol in rats.

This protocol describes a novel and efficient method to quickly initiate operant responding for ethanol in rats that, contrary to standard methods, does not require water deprivation or saccharin/sucrose fading to initiate responding.

水剥奪、サッカリンフェージングまたは拡張アクセストレーニングなしでラットにおけるエタノールの補強性を評価するための方法

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods ...

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson&#39;s lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way.

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

Hemiparkinsonianラットにおける脳深部刺激効果のモーターの成果を評価するための新しいアプローチ：階段室とシリンダーテスト

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

Visualization Method for Proprioceptive Drift on a 2D Plane Using Support Vector Machine

Proprioceptive drift, which is a perceptual shift in body-part position from the unseen real body to a visible body-like image, has been measured as the behavioral correlate for the sense of ownership. Previously, the estimation of proprioceptive drift was limited to one spatial dimension, such as height, width, or depth. As the hand can move freely in 3D, measuring proprioceptive drift in only one dimension is not sufficient for the estimation of the drift in real life situations. In this article, we provide a novel method to estimate proprioceptive drift on a 2D plane using the mirror illusion by combining an objective behavioral measurement (hand position tracking) and subjective, phenomenological assessment (subjective assessment of hand position and questionnaire) with a sophisticated machine learning approach. This technique permits not only an investigation of the underlying mechanisms of the sense of ownership and agency but also assists in the rehabilitation of a missing or paralyzed limb and in the design rules of real-time control systems with a self-body-like usability, in which the operator controls the system as if it were part of his/her own body.

This article describes a novel method to estimate proprioceptive drift on a 2D plane using the mirror illusion and combining a psychophysical procedure with an analysis using machine learning.

サポートベクターマシンを利用して2次元平面上の固有受容ドリフトのための可視化手法

Proprioceptive drift, which is a perceptual shift in body-part position from the unseen real body to a visible body-like image, has been measured as the ...

How to Use the H1 Deep Transcranial Magnetic Stimulation Coil for Conditions Other than Depression

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The coils are made of soft copper windings in multiple planes that lie adjacent to the skull. They are located within a special helmet so that their magnetic fields combine and improve depth penetration. The H1 dTMS coil is designed to stimulate bilateral prefrontal cortices with greater effective stimulation over the left than the right. By positioning the left side of the coil close to the left dorsolateral prefrontal cortex (DLPFC), the H1 coil was used in a multisite study, leading to FDA approval for treatment-resistant depression. In this same position, the H1 coil was also explored as a possible treatment for negative symptoms of schizophrenia, bipolar depression, and migraine. When moved to different positions over the subject's skull, the H1 coil was also explored as a possible treatment for other conditions. Such manipulation of the H1 coil was demonstrated for PTSD and alcohol dependence by positioning it over the medial prefrontal cortex (mPFC), for anxiety by positioning it over the right prefrontal cortex (rPFC), for auditory hallucinations and tinnitus by positioning it over the temporoparietal junction (TPJ), and for Parkinson's and fatigue from multiple sclerosis (MS) by positioning it over the motor cortex (MC) and PFC. Corresponding electrical field diagrams measured with an oscilloscope through a saline-filled head are included.

The H1 deep transcranial magnetic stimulation coil is FDA-cleared for the treatment of depression. We demonstrate how to utilize the H1 for other conditions, such as auditory hallucinations and PTSD, by moving the helmet to different locations over the subject's skull.

うつ病以外の条件のためにH1ディープ経頭蓋磁気刺激コイルを使用する方法

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The ...

A Within-subjects Experimental Protocol to Assess the Effects of Social Input on Infant EEG

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants socially interact. Electroencephalography (EEG) power is an advantageous technique to assess infant functional neural activation. However, many studies record infant EEG only during one baseline condition. This protocol describes a paradigm that is designed to comprehensively assess infant EEG activity in both social and nonsocial contexts as well as tease apart how different types of social inputs differentially relate to infant EEG. The within-subjects paradigm includes four controlled conditions. In the nonsocial condition, infants view objects on computer screens. The joint attention condition involves an experimenter directing the infant's attention to pictures. The joint attention condition includes three types of social input: language, face-to-face interaction, and the presence of joint attention. Differences in infant EEG between the nonsocial and joint attention conditions could be due to any of these three types of input. Therefore, two additional conditions (one with language input while the experimenter is hidden behind a screen and one with face-to-face interaction) were included to assess the driving contextual factors in patterns of infant neural activation. Representative results demonstrate that infant EEG power varied by condition, both overall and differentially by brain region, supporting the functional nature of infant EEG power. This technique is advantageous in that it includes conditions that are clearly social or nonsocial and allows for examination of how specific types of social input relate to EEG power. This paradigm can be used to assess how individual differences in age, affect, socioeconomic status, and parent-infant interaction quality relate to the development of the social brain. Based on the demonstrated functional nature of infant EEG power, future studies should consider the role of EEG recording context and design conditions that are clearly social or nonsocial.

This novel protocol is designed to assess the neural bases of social interaction in infants. The paradigm is designed to tease apart how various social inputs such as language, joint attention, and face-to-face interaction relate to infant neural activation. Infant EEG power is recorded during both social and nonsocial conditions.

幼児EEGに関する社会入力の効果を評価するために、被験者内実験プロトコール

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants ...

Simultaneous Transcranial Alternating Current Stimulation and Functional Magnetic Resonance Imaging

Transcranial alternating current stimulation (tACS) is a promising tool for noninvasive investigation of brain oscillations. TACS employs frequency-specific stimulation of the human brain through current applied to the scalp with surface electrodes. Most current knowledge of the technique is based on behavioral studies; thus, combining the method with brain imaging holds potential to better understand the mechanisms of tACS. Because of electrical and susceptibility artifacts, combining tACS with brain imaging can be challenging, however, one brain imaging technique that is well suited to be applied simultaneously with tACS is functional magnetic resonance imaging (fMRI). In our lab, we have successfully combined tACS with simultaneous fMRI measurements to show that tACS effects are state, current, and frequency dependent, and that modulation of brain activity is not limited to the area directly below the electrodes. This article describes a safe and reliable setup for applying tACS simultaneously with visual task fMRI studies, which can lend to understanding oscillatory brain function as well as the effects of tACS on the brain.

Transcranial alternating current stimulation (tACS) is a promising tool for noninvasive investigation of brain oscillations, though its effects are not completely understood. This article describes a safe and reliable setup for applying tACS simultaneously with functional magnetic resonance imaging, which can increase understanding oscillatory brain function and effects of tACS.