FDは、統合失調症とうつ病に関する研究とカナダの精神疾患研究財団からCPRF賞のための米国国立アライアンスから若手研究者賞によってサポートされていました。

I.作業の設計、刺激、および実験プロトコール<ol><li>このプロトコルの基本的なタスクは、新規タスクは無関係感情とニュートラルdistractersが覚書及びプローブ（元のタスクを示す図については図1を参照）間の遅延間隔の間に提示される遅延応答WMのタスク、です。参加者はこのタスクを実行中にイベント関連fMRIデータが記録されます。実際distractersのスクランブルバージョンも同一の基本的な特性（例えば、空間周波数と輝度を）持っている知覚コントロールとして使用することができます。 </li></ol><img src="/files/ftp_upload/2434/2434fig1.jpg" alt="図1" /> 図1。気晴らしと遅延-応答ワーキングメモリータスク （6から、許可を得て） の一般的な図 。 IMPACを増加させるために3つの面が強く背執行システムを従事するために覚書に使用されている、と小説distractersのペアが使用されます。WMのパフォーマンスと脳活動に関する感情的な気晴らしのt。感情的なdistractersの影響も（図示せず）色で画像を提示することによって増加し、同様の感情と意味内容とdistractersを組み合わせることができます。この文脈では、細心の注意をも可能困惑を導入しないように、そのような明るさと空間周波数15などの基本的なプロパティ、で感情的中立の画像を一致させるに注意を払う必要があります。参加者はまだdistractersの処理中にWMのタスクに焦点を維持するため、および応答ボタン（1 =旧、2 =新規）を押すことにより、プローブに迅速かつ的確な対応を行うように指示されます。刺激提示のために、我々はCIGAL（使用<a href="http://www.nitrc.org/projects/cigal/">http://www.nitrc.org/projects/cigal/を</a> ）。覚書とプローブは、カラーまたは白黒で表示することができます。 <ol start="2"><li>それは、覚書の顔の性別は、バランスのとれた男性の割合（50％）とfを持っていることをお勧めしますemales（50％）。同様のバランスのとれた割合は、（50％） 古いものと新しい （50％）、プローブ用にお勧めします。 WMのタスクの難しさこれらの比率を変えることによって変えることができるおよび/またはその他の要因を変えることによって - 例えば、プローブと同じ覚書及びそれらの類似性からの面の間で顔の特徴の類似性、および/または存在/不在を操作することによって覚書内に追加可能なエキストラ-顔貌（映画も参照してください）​​。顔に加えて、他の刺激にも覚書とプローブ9として使用することができます。 </li><li>それは&quot;スローペース&quot;設計堅牢なfMRIの信号も少ない試行で得られるように（6から補足資料を参照）、その安定性を与えられたが、条件6 30〜40臨床試験、11は 、この設計で使用することをお勧めします。これは〜1.5〜2時間のfMRIデータの収集が可能になります。、健康と臨床の両方の参加者で使用することは可能である。試験の比較的低い数字のために、そのわずかな欠点にもかかわらず&quot;ペースの速い&quot;のデザインに比べて関与できるよう、このデザインは機能的にも有利な、より安定した単一試行fMRIの信号と個々の試験に関連する信号のより良い分離を得るのと試験刺激/フェーズ内での利点があります接続性の分析。 </li><li> distractersの種類の変化も調査し、対象となる集団の目標に応じてそれを適応することによって、この設計の多様性に貢献しています。オリジナルデザインの6の感情とニュートラルdistractersは国際情動写真システム16から選ばれたが、同様の効果がdistracters 12と、および/ ​​またはでWMのタスクの感度を増加させる操作と効果的な他の小説の刺激を得ることができます。動作の違い（例えば、また、その応答で参加者の信頼を評価することで）11を検出。 </li><li>例えば、戦後のVEの最近の研究で12でまたは心的外傷後ストレス障害（PTSD）のないteransは、一般的な否定的な感情を誘発する感情的な個別行動計画の画像は、戦闘関連の写真に置き換えられた。これらの写真は、より具体的に戦闘関連のトラウマにリンクされているため、特にPTSD群では戦闘に暴露したコホートでより効果的distracters、なるされている感情を誘発することが期待されていた。また、特定の否定的な感情（例えば、不安を）誘発する刺激または感情的に正の刺激もdistractersとして使用することができる。例えば、恐ろしい表現を表示すると、社会不安を誘発するため、WM 11日に一時的な不安を誘発する気晴らしの影響を調査するのに有効である可能性に直面している。また、同様の効果が正のdistracters 17で見つけることができます。 </li><li>最後に、その他の措置（例えば、行動および人格に関連）と一緒にこのパラダイムは、異なる脳の活動と個々の関係を調査するために使用することができます<html>このタスク8、10、11の認知能力に影響を与える様々な面でences。 </li></ol> II。スキャンのために件名の準備すべての参加者は、倫理委員会によって承認されるべき実験的なプロトコルを、実行する前に書面によるインフォームドコンセントを提供する必要があります。 前にスキャン部屋に入る<ol><li>スキャンの日に、参加者の現在の感情状態は気晴らしとWMのタスクのムードの効果を制御するために、評価される。ポストスキャンの評価と併せて、これらの初期の評価も研究11に参加の結果として、気分の変化を画面に使用することができます。 </li><li>スキャンの前に、参加者は、スキャンの手順の詳細に通知され、行動課題のための具体的な指示が与えられます。参加者はまた、タスクを理解するために、短い練習セッションを完了します。 </li></ol>e_step&quot;&gt;スキャンの部屋に入る<ol start="3"><li>参加者は、スキャン中に快適性を確保し、動きを最小限に抑えるため、ヘッドのための追加のクッションと、スキャニングベッドに仰臥位にあります。さらにヘッドの動きを最小限に抑えるために、テープの長さの非粘着面は、被験者の前頭部の周りに軽くラップされることがあります。被験者は、MRIスキャン中に実験者と通信するために耳の保護だけでなく、分離のヘッドフォンを与えられている。 </li><li>被験者の右手は、応答のボックスに快適に配置されている。データの収集を開始する前に、それは応答ボタンが正しく動作して被験者が刺激の提示には明らかに画面の投影を見ることができることを確認するために重要です。緊急停止ボタンは、被験者がスキャナを停止するには、どんな緊急の必要性を示すことができるように、近くに配置されます。 </li></ol>スキャンセッションに続いて<ol start="5"><li>追加のタスクは、さらなる行動assessmenのために使用することができますTS - たとえば、定格で、distractersへの参加者の感受性を決定するために感情価distractersの/強度および/またはdistractersの主観的に知覚される散漫。これらの評価は、そのスキャン中に使用される感情刺激の主観的な認識は、文献に示されている以前の効果を複製し、定格内の個々の違いが認知6日の感情の有害な作用を媒介する神経機構に与える影響を調査するために使用できるようにするために使用することができます。 、8。 </li><li>性格特性（例えば、特性不安、感情的な反応性）の評価も11をスキャンする前に実行されていない場合、MRIスキャンの後に行うことができます。 </li></ol> III。データの記録および分析スキャンパラメータオリジナルの研究6では、我々はMRI録音用の4テスラゼネラルエレクトリックのスキャナを使用してMRIデータを収集し、より多くのREC用タスクのENT版我々はまた、1.5 Tスキャナ11とMRIデータを収集することに成功した。 30機能的なスライスの4Tスキャナ、シリーズで（ボクセルサイズ= 4 × 4 × 4 mm）が軸方向に逆スパイラルのパルスシーケンスを用いて取得された（TR = 2000ミリ秒、TE = 31ミリ秒; = 256 × 256ミリメートルビューのフィールド） 、こうしてフル脳カバーすることができます。同様に、28機能的なスライスの1.5スキャナ、シリーズの（ボクセルサイズ= 4 × 4 × 4 mm）は、軸方向にechoplanarシーケンスを使用して得られた（TR = 2000ミリ秒、TE = 40ミリ秒、視野= 256 × 256 mmのフィールド）。 （;解剖学-機能的な比= 4:1の面内分解能= 1 mm 2）の高分解能構造の画像は、軸方向に買収された。 データ解析 ：我々は、統計的パラメトリックマッピング（SPM使用<a href="http://www.fil.ion.ucl.ac.uk/spm/">http://www.fil.ion.ucl.ac.uk/spm/</a>社内MATLABベースのツールと組み合わせて）。前処理は、典型的な手順が含まれます：品質保証*、TRlignment、モーション補正、共同登録、正規化、および平滑化（8 × 8 × 8 mmのカーネルを使用して）、*基本的な品質保証データの目視検査を関与、参加者と運動に関連する成果物の総動きを検出するためにデータだけでなく、MR信号の異常なスパイクを持つボリュームの識別。個人およびグループレベルの統計分析は、不正解のタイプ（感情的な対中立気晴らし）によると脳活動の比較を含む。また、散漫性の主観的または客観的な措置（例えば、感情と散漫性評価とワーキングメモリの性能）6,8,11及び/または得点のインデックスの人格対策と脳画像データの相関が（例えば、特性不安）11はまた、実行することができます調査の方法脳の活動は、それらの措置の個人差との共同によって異なります。このプロトコルを使用して我々の研究のすべての分析は通常、WHE、遅延周期の間に観察された活動に焦点を当てているn個のdistractersが発表、しかし活動（例えば、プローブ）他のイベントにも調査することができる時間は、ロックされています。 IV。代表的な結果<img src="/files/ftp_upload/2434/2434fig2.jpg" alt="図2" /> 図2。感情的な気晴らしの存在下での腹側対背脳のシステムの活動の反対パターン （6から、許可を得て）。このような背外側前頭前皮質のような背幹部の脳領域（青い塊）、で減少した活動を作り出している間感情distractersは、そのような腹前頭前野（vlPFC）と扁桃体（図示せず）などの腹側情動の脳領域（赤い塊）に増強された活性を生産（DLPFC）と横方向の頭頂皮質（LPC）。中央の画像は、横方向に表示されている高解像度の脳画像に重ね合わせ、少なくとも邪魔条件（すなわち、感情的な対スクランブル）対ほとんどの間に直接的なコントラストの活性化マップを、示しています。右半球の眺め。脳の画像の下部にある色の水平バーが活性化マップのt値の勾配を示している。線グラフは、代表的な背側と腹側脳領域（色分けされた矢印で示される）の活動の時間経過を示す。 x軸上にある灰色の長方形のボックスは発症と持続覚書の、distracters、およびプローブを、それぞれ示している。 FFG =紡錘状回。

<ol>
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利害の衝突は宣言されません。

この実験的なデザインは、現在進行中の認知過程で感情的な気晴らしの有害な影響がHotEmo腹側神経系およびColdEx背側システムの間で相互変調を伴うという初期の脳機能イメージングの証拠を提供した。この背腹解離は、感情的な気晴らし6の存在下で障害WMのパフォーマンスにリンクした体系的に通常の8-11、臨床12-14に複製されており、このような睡眠不?...

brain imaging investigation of the impairing effect of emotion on cognition

感情は、両方を向上させる （例えば、感情的なイベントのためのよりよいメモリ）とを損なう （例えば、増加した感情的な散漫性）の影響を（1レビュー）行使によって認知に影響を与える可能性があります。感情の記憶増強効果（も1、3-5を参照）の神経相関の調査を可能にする方法を説明する2私たちの最近のプロトコルを補完し、ここではの有害な影響の神経相関の調査を可能にするプロトコルを提示認知上の感情。この方法の主な特徴は、それが&quot;ホット&quot;な感情処理（HotEmoシステム）に関わる腹側神経系の活性との間の相互変調の識別、および背側システムは、より高いレベルの&quot;コールド&quot;認知/エグゼクティブに関与できることです認知能力と行動の個人差（1レビュー）にリンクされている処理（ColdExシステム）、。その初期introdu以来、ction 6、このデザインは、ワーキングメモリ（WM）を中心に、認知上の感情的な気晴らしの有害な影響の神経相関に関する様々な側面の解明に特に汎用性と影響力の実証、およびそのような気晴らし7,11への対処をしている、両方8月11日健康と臨床の参加者12〜14インチ

Watch this Scientific Journal Video about Brain Imaging Investigation of the Impairing Effect of Emotion on Cognition at JoVE.com

Brain Imaging Investigation of the Impairing Effect of Emotion on Cognition

我々は、機能的磁気共鳴画像法を用いて、認知の感情の有害な影響を媒介する神経機構の調査を可能にするプロトコルを示す。このプロトコルは、健康と臨床の両方の参加者と一緒に使用することができます。

認知に関する情動の損なう効果の脳イメージング研究

Emotions can impact cognition by exerting both enhancing (e.g., better memory for emotional events) and impairing (e.g., increased emotional ...

brain-imaging-investigation-impairing-effect-emotion-on

Research

JoVE Journal

Neuroscience

16.0K ビュー.  University of Alberta. 我々は、機能的磁気共鳴画像法を用いて、認知の感情の有害な影響を媒介する神経機構の調査を可能にするプロトコルを示す。このプロトコルは、健康と臨床の両方の参加者と一緒に使用することができます。

ビデオ: Brain Imaging Investigation of the Impairing Effect of Emotion on Cognition

State-Dependency Effects on TMS:  A Look at Motive Phosphene Behavior

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.1,2 Within the field of TMS, the term state dependency refers to the initial, baseline condition of the particular neural region targeted for stimulation. As can be inferred, the effects of TMS can (and do) vary according to this primary susceptibility and responsiveness of the targeted cortical area.3,4,5

In this experiment, we will examine this concept of state dependency through the elicitation and subjective experience of motive phosphenes. Phosphenes are visually perceived flashes of small lights triggered by electromagnetic pulses to the visual cortex. These small lights can assume varied characteristics depending upon which type of visual cortex is being stimulated. In this particular study, we will be targeting motive phosphenes as elicited through the stimulation of V1/V2 and the V5/MT+ complex visual regions.6

In this article, we examine the effects of visually relevant state dependency on TMS induced motive phosphenic presentations.

TMSの状態 - 依存性の効果：動機の閃光の挙動を見

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate ...

神経科学

Brain Imaging Investigation of the Neural Correlates of Observing Virtual Social Interactions

The ability to gauge social interactions is crucial in the assessment of others&#x2019; intentions. Factors such as facial expressions and body language affect our decisions in personal and professional life alike 1. These "friend or foe" judgements are often based on first impressions, which in turn may affect our decisions to "approach or avoid". Previous studies investigating the neural correlates of social cognition tended to use static facial stimuli 2. Here, we illustrate an experimental design in which whole-body animated characters were used in conjunction with functional magnetic resonance imaging (fMRI) recordings. Fifteen participants were presented with short movie-clips of guest-host interactions in a business setting, while fMRI data were recorded; at the end of each movie, participants also provided ratings of the host behaviour. This design mimics more closely real-life situations, and hence may contribute to better understanding of the neural mechanisms of social interactions in healthy behaviour, and to gaining insight into possible causes of deficits in social behaviour in such clinical conditions as social anxiety and autism 3.

This article demonstrates an experimental design in which whole-body animated characters are used in conjunction with functional magnetic resonance imaging (fMRI) to investigate the neural correlates of observing virtual social interactions.

仮想社会的相互作用を観察するの神経相関の脳イメージング研究

The ability to gauge social interactions is crucial in the assessment of others&#x2019; intentions. Factors such as facial expressions and body language ...

Brain Imaging Investigation of the Neural Correlates of Emotional Autobiographical Recollection

Recollection of emotional autobiographical memories (AMs) is important to healthy cognitive and affective functioning 1 - remembering positive AMs is associated with increased personal well-being and self-esteem 2, whereas remembering and ruminating on negative AMs may lead to affective disorders 3. Although significant progress has been made in understanding the brain mechanisms underlying AM retrieval in general (reviewed in 4, 5), less is known about the effect of emotion on the subjective re-experience of AMs and the associated neural correlates. This is in part due to the fact that, unlike the investigations of the emotion effect on memory for laboratory-based microevents (reviewed in 6, 7-9), often times AM studies do not have a clear focus on the emotional aspects of remembering personal events (but see 10). Here, we present a protocol that allows investigation of the neural correlates of recollecting emotional AMs using functional magnetic resonance imaging (fMRI). Cues for these memories are collected prior to scanning by means of an autobiographical memory questionnaire (AMQ), therefore allowing for proper selection of emotional AMs based on their phenomenological properties (i.e., intensity, vividness, personal significance). This protocol can be used in healthy and clinical populations alike.

We present a protocol that allows investigation of the neural correlates of recollecting emotional autobiographical memories, using functional magnetic resonance imaging. This protocol can be used with both healthy and clinical participants.

感情的な自伝追憶の神経相関の脳イメージング研究

Recollection of emotional autobiographical memories (AMs) is important to healthy cognitive and affective functioning 1 - remembering positive AMs is ...

Brain Imaging Investigation of the Neural Correlates of Emotion Regulation

The ability to control/regulate emotions is an important coping mechanism in the face of emotionally stressful situations. Although significant progress has been made in understanding conscious/deliberate emotion regulation (ER), less is known about non-conscious/automatic ER and the associated neural correlates. This is in part due to the problems inherent in the unitary concepts of automatic and conscious processing1. Here, we present a protocol that allows investigation of the neural correlates of both deliberate and automatic ER using functional magnetic resonance imaging (fMRI). This protocol allows new avenues of inquiry into various aspects of ER. For instance, the experimental design allows manipulation of the goal to regulate emotion (conscious vs. non-conscious), as well as the intensity of the emotional challenge (high vs. low). Moreover, it allows investigation of both immediate (emotion perception) and long-term effects (emotional memory) of ER strategies on emotion processing. Therefore, this protocol may contribute to better understanding of the neural mechanisms of emotion regulation in healthy behaviour, and to gaining insight into possible causes of deficits in depression and anxiety disorders in which emotion dysregulation is often among the core debilitating features.

We present a protocol that allows investigation of the neural correlates of deliberate and automatic emotion regulation, using functional magnetic resonance imaging. This protocol can be used in healthy participants, both young and older, as well as in clinical patients.

情動表出の制御の神経相関の脳イメージング研究

The ability to control/regulate emotions is an important coping mechanism in the face of emotionally stressful situations. Although significant progress ...

Brain Imaging Investigation of the Memory-Enhancing Effect of Emotion

Emotional events tend to be better remembered than non-emotional events1,2. One goal of cognitive and affective neuroscientists is 
to understand the neural mechanisms underlying this enhancing effect of emotion on memory. A method that has proven particularly influential in the 
investigation of the memory-enhancing effect of emotion is the so-called subsequent memory paradigm (SMP). This method was originally used to investigate the 
neural correlates of non-emotional memories3, and more recently we and others also applied it successfully to studies of emotional memory (reviewed in4, 5-7). 
Here, we describe a protocol that allows investigation of the neural correlates of the memory-enhancing effect of emotion using the SMP in conjunction with 
event-related functional magnetic resonance imaging (fMRI). An important feature of the SMP is that it allows separation of brain activity specifically 
associated with memory from more general activity associated with perception. Moreover, in the context of investigating the impact of emotional stimuli, 
SMP allows identification of brain regions whose activity is susceptible to emotional modulation of both general/perceptual and memory-specific processing. 
This protocol can be used in healthy subjects8-15, as well as in clinical patients where there are alterations in the neural correlates of emotion perception 
and biases in remembering emotional events, such as those suffering from depression and post-traumatic stress disorder (PTSD)16, 17.

We present a protocol that uses functional magnetic resonance imaging to investigate the neural correlates of the memory-enhancing effect of emotion. This protocol allows identification of brain activity specifically linked to memory-related processing, contrary to more general perceptual processing, and can be used with healthy and clinical populations.

感情の記憶増強効果の脳イメージング研究

Emotional events tend to be better remembered than non-emotional events1,2. One goal of cognitive and affective neuroscientists is 
to understand the ...

Enabling High Grayscale Resolution Displays and Accurate Response Time Measurements on Conventional Computers

Display systems based on conventional computer graphics cards are capable of generating images with 8-bit gray level resolution. However, most experiments in vision research require displays with more than 12 bits of luminance resolution. Several solutions are available. Bit++ 1 and DataPixx 2 use the Digital Visual Interface (DVI) output from graphics cards and high resolution (14 or 16-bit) digital-to-analog converters to drive analog display devices. The VideoSwitcher 3 described here combines analog video signals from the red and blue channels of graphics cards with different weights using a passive resister network 4 and an active circuit to deliver identical video signals to the three channels of color monitors. The method provides an inexpensive way to enable high-resolution monochromatic displays using conventional graphics cards and analog monitors. It can also provide trigger signals that can be used to mark stimulus onsets, making it easy to synchronize visual displays with physiological recordings or response time measurements.
Although computer keyboards and mice are frequently used in measuring response times (RT), the accuracy of these measurements is quite low. The RTbox is a specialized hardware and software solution for accurate RT measurements. Connected to the host computer through a USB connection, the driver of the RTbox is compatible with all conventional operating systems. It uses a microprocessor and high-resolution clock to record the identities and timing of button events, which are buffered until the host computer retrieves them. The recorded button events are not affected by potential timing uncertainties or biases associated with data transmission and processing in the host computer. The asynchronous storage greatly simplifies the design of user programs. Several methods are available to synchronize the clocks of the RTbox and the host computer. The RTbox can also receive external triggers and be used to measure RT with respect to external events. 
Both VideoSwitcher and RTbox are available for users to purchase. The relevant information and many demonstration programs can be found at <a href="http://lobes.usc.edu/">http://lobes.usc.edu/</a>.

Conventional computer hardware can not generate visual stimuli with sufficiently high grayscale resolution and measure response times with sufficient accuracy. We describe how to use the VideoSwitcher to produce high-resolution monochromatic displays, and the RTbox to measure response times with high accuracy on conventional computer hardware.

有効にする高解像度を表示し、従来のコンピュータ上で正確な応答時間の測定値をグレースケール

Display systems based on conventional computer graphics cards are capable of generating images with 8-bit gray level resolution. However, most experiments ...

Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when studying the brain, as the functional role that a brain area fulfills may be largely defined by its connections to other brain areas. In this report, we describe a novel, non-invasive approach for relating brain structure and function using magnetic resonance imaging (MRI). This approach, a combination of structural imaging of long-range fiber connections and functional imaging data, is illustrated in two distinct cognitive domains, visual attention and face perception. Structural imaging is performed with diffusion-weighted imaging (DWI) and fiber tractography, which track the diffusion of water molecules along white-matter fiber tracts in the brain (Figure 1). By visualizing these fiber tracts, we are able to investigate the long-range connective architecture of the brain. The results compare favorably with one of the most widely-used techniques in DWI, diffusion tensor imaging (DTI). DTI is unable to resolve complex configurations of fiber tracts, limiting its utility for constructing detailed, anatomically-informed models of brain function. In contrast, our analyses reproduce known neuroanatomy with precision and accuracy. This advantage is partly due to data acquisition procedures: while many DTI protocols measure diffusion in a small number of directions (e.g., 6 or 12), we employ a diffusion spectrum imaging (DSI)1, 2 protocol which assesses diffusion in 257 directions and at a range of magnetic gradient strengths. Moreover, DSI data allow us to use more sophisticated methods for reconstructing acquired data. In two experiments (visual attention and face perception), tractography reveals that co-active areas of the human brain are anatomically connected, supporting extant hypotheses that they form functional networks. DWI allows us to create a "circuit diagram" and reproduce it on an individual-subject basis, for the purpose of monitoring task-relevant brain activity in networks of interest.

We describe a novel approach for simultaneous analysis of brain function and structure using magnetic resonance imaging (MRI). We assess brain structure with high-resolution diffusion-weighted imaging and white-matter fiber tractography. Unlike standard structural MRI, these techniques allow us to directly relate anatomical connectivity to functional properties of brain networks.

fMRIと拡散強調画像を用いた脳の構造と機能の同時分析

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when ...

In Vivo Two-photon Imaging Of Experience-dependent Molecular Changes In Cortical Neurons

The brain's ability to change in response to experience is essential for healthy brain function, and abnormalities in this process contribute to a variety of brain disorders1,2. To better understand the mechanisms by which brain circuits react to an animal's experience requires the ability to monitor the experience-dependent molecular changes in a given set of neurons, over a prolonged period of time, in the live animal. While experience and associated neural activity is known to trigger gene expression changes in neurons1,2, most of the methods to detect such changes do not allow repeated observation of the same neurons over multiple days or do not have sufficient resolution to observe individual neurons3,4. Here, we describe a method that combines in vivo two-photon microscopy with a genetically encoded fluorescent reporter to track experience-dependent gene expression changes in individual cortical neurons over the course of day-to-day experience. 
One of the well-established experience-dependent genes is Activity-regulated cytoskeletal associated protein (Arc)5,6. The transcription of Arc is rapidly and highly induced by intensified neuronal activity3, and its protein product regulates the endocytosis of glutamate receptors and long-term synaptic plasticity7. The expression of Arc has been widely used as a molecular marker to map neuronal circuits involved in specific behaviors3. In most of those studies, Arc expression was detected by in situ hybridization or immunohistochemistry in fixed brain sections. Although those methods revealed that the expression of Arc was localized to a subset of excitatory neurons after behavioral experience, how the cellular patterns of Arc expression might change with multiple episodes of repeated or distinctive experiences over days was not investigated. 
In vivo two-photon microscopy offers a powerful way to examine experience-dependent cellular changes in the living brain8,9. To enable the examination of Arc expression in live neurons by two-photon microscopy, we previously generated a knock-in mouse line in which a GFP reporter is placed under the control of the endogenous Arc promoter10. This protocol describes the surgical preparations and imaging procedures for tracking experience-dependent Arc-GFP expression patterns in neuronal ensembles in the live animal. In this method, chronic cranial windows were first implanted in Arc-GFP mice over the cortical regions of interest. Those animals were then repeatedly imaged by two-photon microscopy after desired behavioral paradigms over the course of several days. This method may be generally applicable to animals carrying other fluorescent reporters of experience-dependent molecular changes4.

In Vivo Two-photon Imaging Of Experience-dependent Molecular Changes In Cortical Neurons

Experience-dependent molecular changes in neurons are essential for the brain's ability to adapt in response to behavioral challenges. An in vivo two-photon imaging method is described here that allows the tracking of such molecular changes in individual cortical neurons through genetically encoded reporters.

皮質ニューロンにおける経験依存性分子の変化の in vivo二光子イメージングにおける

The brain's ability to change in response to experience is essential for healthy brain function, and abnormalities in this process contribute to a variety ...

A Dual Tracer PET-MRI Protocol for the Quantitative Measure of Regional Brain Energy Substrates Uptake in the Rat

We present a method for comparing the uptake of the brain&#39;s two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the rat. The developed method is a small-animal positron emission tomography (PET) protocol, in which&#160;11C-AcAc and 18F-fluorodeoxyglucose (18F-FDG) are injected sequentially in each animal. This dual tracer PET acquisition is possible because of the short half-life of 11C (20.4 min). The rats also undergo a magnetic resonance imaging (MRI) acquisition seven days before the PET protocol. Prior to image analysis, PET and MRI images are coregistered to allow the measurement of regional cerebral uptake (cortex, hippocampus, striatum, and cerebellum). A quantitative measure of 11C-AcAc and 18F-FDG brain uptake (cerebral metabolic rate; &#956;mol/100 g/min) is determined by kinetic modeling using the image-derived input function (IDIF) method. Our new dual tracer PET protocol is robust and flexible; the two tracers used can be replaced by different radiotracers to evaluate other processes in the brain. Moreover, our protocol is applicable to the study of brain fuel supply in multiple conditions such as normal aging and neurodegenerative pathologies such as Alzheimer&#39;s and Parkinson&#39;s diseases.

Small-animal positron emission tomography enables the assessment of the brain&#39;s two main energy substrates:&#160;glucose and ketones. In the present method, 11C-acetoacetate and 18F-fluorodeoxyglucose are injected sequentially in each animal, and their uptake is measured quantitatively in specific brain regions determined from the magnetic resonance images.

We present a method for comparing the uptake of the brain&#39;s two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the ...

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

Transcranial Alternating Current Stimulation (tACS) allows the modulation of cortical excitability in a frequency-specific fashion. Here we show a unique approach which combines online tACS with single pulse Transcranial Magnetic Stimulation (TMS) in order to "probe" cortical excitability by means of Motor Evoked Potentials.

経頭蓋交流電流刺激オンライン結合による一次運動野の経頭蓋磁気刺激の効果

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...