Questa ricerca è stata sostenuta da sovvenzioni R01-MH090127, P30-MH089868 dell&#39;Istituto Nazionale di Salute Mentale e il numero premio UL1TR001120 dal Centro Nazionale per l&#39;Avanzamento delle Scienze traslazionale. Il contenuto è di esclusiva responsabilità degli autori e non rappresentano necessariamente il punto di vista ufficiale della NIMH o NCATS. Inoltre, vorremmo riconoscere con gratitudine il dottor David Morilak per la sua preziosa esperienza nel guidare lo sviluppo del metodo presto.

NOTA: Gli animali utilizzati in questo studio sono di sesso maschile C57Bl / 6J tra i 4 ei 6 mesi di età per ottenere risultati ottimali. I topi vengono mantenuti in un ciclo luce di retromarcia per testarle comodamente durante la fase attiva (scuro). Se il comportamento viene eseguito in una stanza separata dal corpo, i topi sono ammessi almeno 1 ora per acclimatarsi dopo il trasporto a sala prove. Test comportamentale viene effettuata in condizioni di luce rossa minimizzare i disagi alla normale attività dei topi il meno possibile, pur consentendo lo sperimentatore adeguata illuminazione di monitorare visivamente la sessione di test. NOTA: Tutti gli aspetti della procedura sperimentale qui descritta sono stati effettuati in accordo con la guida per la cura e l&#39;uso di animali da laboratorio, 8 ° edizione (NRC) e sono stati approvati dalla cura e l&#39;uso degli animali Comitato Istituzionale presso l&#39;Università del Texas Health Science Center at San Antonio. <ol><li> Riempire stampini in ceramica (non-poroso; 1.5 &quot;x 2.5 profondità &#39;di diametro), a bordo interno con scavo medio (circa 1&quot; dal basso); turni di carta filtro taglia a metà e attaccata al suo interno posteriore del ramekin (Figura 1A) </li><li> Rompere leggermente zuccherato cereali secchi colazione (cibo ricompensa) - Honey Nut o varietà confetti, in circa 20 pezzi mg per le fasi di acclimatazione, di formazione e di prova. </li><li> Fare un set attenzionale spostamento compito (AST) camera (Figura 1B): Acclimatare treno e testare ogni mouse nelle singole camere; consiglia produzione di almeno 8 camere. <ol><li> Costruire un 12 &quot;x 8&quot; x 7 &quot;camera di AST; pareti e cancelletto di partenza fatte opaco acrilico bianco che è facile da pulire con il 70% di etanolo. Lo stile ghigliottina, cancello partenza rimovibile separa camera in una zona di attesa (5 &quot;x 8&quot;) e l&#39;area di test (7 &quot;x 8&quot;). </li><li> Includere un Clear 5221; x7 &quot;amovibile che separa due lati della zona di prova in modo uniforme; tagliare tre ¼ &quot;diametro buca in parte inferiore del divisorio per consentire l&#39;accesso fiuto, distanziati 1&quot; a parte e 1 &quot;dalla parte anteriore della partizione (Figura 1C). </li></ol></li></ol> 2. Panoramica della procedura (Figura 2) <ol><li> Prima di AST, topi casa individualmente e permettere loro di adattarsi a un ciclo di luce d&#39;inversione per almeno una settimana. </li><li> Ambientarsi, treno e testare ogni animale in singole camere di test. Assegnare ciascuna camera ad un mouse e pulire con il 70% di etanolo dopo aver terminato l&#39;ultimo giorno di test. Questo ridurrà al minimo lo stress durante i test, rendendo l&#39;odore da camera come &quot;casa-gabbia&quot; o &quot;auto&quot;. </li><li> Profumo le pentole test due giorni prima del test per permettere al profumo di dissipare; topi non scaverà in vasi che hanno un odore molto forte. Usando una siringa con un ago 25 G, aggiungere circa 0,1 ml diolio essenziale all&#39;inizio della carta da filtro. </li></ol> 3. Gestione (Giorni 1-8) <ol><li> Maneggiare topi a partire 8 giorni prima del primo giorno di restrizione alimentare. Ciò consentirà di ridurre lo stress associato con la gestione durante i test. </li><li> Pesare e peso corporeo registrare ogni giorno di trattamento. Maneggiare ogni mouse 2-3 minuti al giorno. </li><li> Se più sperimentatori devono essere coinvolti nella verifica di una serie di topi, in modo che ogni sperimentatore partecipa al processo di gestione per aumentare la familiarità con gli sperimentatori e ridurre lo stress e l&#39;ansia con esperienza in materia di formazione o di giorni di test. </li><li> Continuare movimentazione e registrazione pesi tutta la durata della prova. </li></ol> 4. restrizione alimentare (Giorni 9-12) <ol><li> Cominciando 4 giorni prima dell&#39;inizio di acclimatazione, posto mouse su una dieta ristretta per mantenere i topi al 80-85% del loro peso corporeo alimentazione gratuito. Dare 1 grammo di alimento per topo al giorno. Se il peso corporeo scende al di sottol&#39;intervallo specificato dare 2 grammi al giorno fino al ritorno alla gamma appropriata. </li><li> Mettere 2 stampini nella parte anteriore di ogni gabbia casa per consentire topi per acclimatarsi alle pentole di prova. Questi sono gli stessi punti utilizzati per addestrare il mouse per scavare per una ricompensa in cibo. </li><li> Aggiungere 2 grammi di cibo e 1 pezzo di ricompensa alimentare (metà un pezzo di cereali in ciascuna) negli stampini ogni giorno per 4 giorni. </li><li> Se il comportamento deve essere eseguita in una camera separata da quella in cui i topi sono alloggiati, a partire dal giorno 1 di restrizione alimentare, topi trasporto verso la camera di prova per almeno 1 ora al giorno prima di ritornare alla camera dell&#39;alloggiamento per consentire loro di acclimatarsi alla sala prove. </li><li> L&#39;ultimo giorno di restrizione alimentare, prima dell&#39;inizio di acclimatazione, cambiare la biancheria da letto gabbia di casa. La biancheria da letto gabbia non sarà cambiato di nuovo fino a dopo la prova è completa per ridurre lo stress o l&#39;ansia vissuta durante l&#39;allenamento e test (se non assolutamente necessario). </li><li> Manteneretopi sulla restrizione alimentare fino alla fine del test. Nei giorni 13-17, dare da mangiare topi dopo acclimatazione, la formazione, o test sulla base di una stima della quantità di cibo consumato ricompensa (in genere &lt;1 g di pellet alimentare). </li></ol> 5. acclimatazione (Giorni 13-14) <ol><li> Inizio 2 giorni prima dell&#39;inizio della formazione, eseguire acclimatazione durante il ciclo di buio sotto una luce rossa. </li><li> Stendere una piccola quantità di biancheria sporca dalla gabbia di casa nella camera, questo ridurrà lo stress di essere in un nuovo ambiente, introducendo un familiare &quot;casa-gabbia&quot; o &quot;sé&quot; odore della camera di prova (stessa camera sarà utilizzato per un singolo mouse per la durata della formazione e test). </li><li> Posizionare un ramekin pulito con acqua nella sala d&#39;attesa della camera; topi tendono a non mangiare se non hanno accesso all&#39;acqua. </li><li> Posizionare le due stampini che sono stati utilizzati per la restrizione alimentare nell&#39;area test con una ricompensa alimentare (~ 20piece cereali mg) in ciascuna. </li><li> Posizionare il mouse nell&#39;area di attesa; rimuovere il cancelletto di partenza e lasciare il mouse per esplorare la camera per 1 ora. </li><li> Continuamente aggiungere ricompense alimentari (~ 20 mg pezzo di cereali) agli stampini vuoti al fine di incoraggiare i topi per esplorare la zona di prova e le pentole frequentemente. </li><li> Assicurarsi che il mouse può vedere sperimentatore tutto il periodo di acclimatazione modo che la presenza dello sperimentatore non è un fattore di stress aggiunto durante la prova. </li></ol> 6. Formazione (Giorno 15) <ol><li> Posizionare il mouse nell&#39;area di attesa. </li><li> Mettere gli stampini vuoti, ognuno contenente una ricompensa alimentare (~ 20 mg pezzo di cereali), nella zona di test e sollevare il cancelletto di partenza. Lasciare il mouse 3 min a recuperare entrambe le ricompense alimentari. Ripetere questa operazione più volte. </li><li> Aggiungere gradualmente assestamento gabbia segatura / mouse per le pentole in prove successive. Lasciare il mouse 3 min per recuperare la ricompensa cibo dal piatto prima di terminare la trial. Una volta che il mouse ha recuperato la ricompensa cibo dal piatto, procedere alla prova successiva. Se il mouse non fa tentativi di scavare una volta la ricompensa cibo è parzialmente coperto, suggerimenti possono essere previste (ad esempio, cospargere di polvere cereali su area della ricompensa alimentare, fare un rientro nella segatura sopra l&#39;area di cibo ricompensa, scoprire una parte del ricompensa alimentare). </li><li> Continuare ad aggiungere segatura / assestamento dopo ogni prova fino a quando la ricompensa cibo è completamente coperto e il mouse dimostra affidabile la capacità di scavare in una pentola piena di trovare la ricompensa cibo. </li><li> Se un mouse non è affidabile dimostrato la capacità di trovare una ricompensa alimentare in una pentola piena in 2 ore di inizio della formazione, continuano ad una seconda giornata di formazione. Mantenere il mouse sulla restrizione alimentare e ripetere la procedura il giorno successivo. </li><li> Se il mouse non scavare un premio cibo dopo due giorni consecutivi, escluderlo dal resto dell&#39;esperimento, e annotare come &quot;impossibile scavare&quot; nel exprecord di erimental. </li></ol> 7. Testing (Giorni 16-17): <ol><li> Il primo giorno, test di discriminazione semplice (SD), la discriminazione composto (CD), inversione (R1), e lo spostamento intra-dimensionali (IDS). </li><li> Il secondo giorno, prova lo spostamento intra-dimensionale 2 (IDS2), spostamento intra-dimensionale 3 (IDS3), inversione di 2 (R2, optional), cambio extra-dimensionale (EDS). </li><li> Coppia supporti e profumi come indicato nella tabella 1. </li><li> Al momento della movimentazione in giornata di test, i topi dare una ricompensa alimentare per evitare una mancanza di attenzione durante i test a causa della fame. Da questo punto fino alla fine della giornata test, non forniscono alcun cibo tranne ricompense per scelte corrette. </li><li> All&#39;inizio del test, usando pinze (limita la diffusione di profumi tra pentole), inserire un pezzo di ricompensa cibo nel piatto che indica una scelta corretta. La ricompensa cibo deve essere completamente coperto dai media (vedi figura 3). Per evitare spunto profumo della ricompensa alimentare, cospargere di polvere o di cerealiver tutti pentole all&#39;inizio della tappa. </li><li> Posizionare il mouse nella zona di attesa con il cancelletto di partenza chiuso. Posizionare i vasi su entrambi i lati della camera di prova. Il processo inizia quando il gate di partenza viene rimosso e il temporizzatore viene avviato. Consentire ogni mouse 3 min per prova a fare una scelta. Registrare la scelta (giusta o sbagliata) e tempo fino il mouse ha fatto una scelta per ogni prova. NOTA: A &quot;scelta&quot; è indicato da un tentativo di scavare in entrambi piatto. Un scavo viene registrata solo come una scelta se il mouse ha spostato i media e infilò il naso abbastanza lontano nello spazio che crea per trovare la ricompensa cibo o abbastanza sfollati del supporto per scoprire la ricompensa cibo. Se il mouse non ha fatto una scelta nel raggio di 3 min, questo viene registrato come scelta (non corretta). </li><li> Una volta scelta è stata fatta per entrambi pentola, togliere la pentola non è stato scelto dalla camera di prova. Se è stata effettuata una scelta corretta, permettere al mouse per terminare la ricompensa cibo prima di rimettere il mouse inl&#39;area di attesa. Se si effettua una scelta errata, permettere al mouse per esplorare la pentola per dimostrare che non vi è alcuna ricompensa alimentare per questa scelta prima di restituire il mouse per la sala d&#39;attesa. </li><li> Alla fine di ogni prova, posizionare il mouse posteriore nell&#39;area di attesa e sostituire il gate di partenza. </li><li> Assicurarsi che il mouse soddisfa il criterio di 8 prove corrette consecutivamente per passare alla successiva fase di AST. Se il mouse non ottiene 8 scelte corrette consecutivamente in 50 prove, non riesce questa fase e non può passare per completare il test. 6 consecutivi non scelte (3 min senza scelta) è una mancata partecipazione e vieta il mouse da passare alla fase successiva. </li></ol>

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	<li>Birrell, J. M., Brown, V. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Medial+frontal+cortex+mediates+perceptual+attentional+set+shifting+in+the+rat.">Medial frontal cortex mediates perceptual attentional set shifting in the rat.</a> J Neurosci. 20 (11), 4320-4324 (2000).</li><li>Garner, J. P., Thogerson, C. M., Wurbel, H., Murray, J. D., Mench, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+neuropsychology:+validation+of+the+Intra-Dimensional+Extra-Dimensional+set+shifting+task+for+mice.">Animal neuropsychology: validation of the Intra-Dimensional Extra-Dimensional set shifting task for mice.</a> Behav Brain Res. 173 (1), 53-61 (2006).</li><li>Nagahara, A. H., Bernot, T., Tuszynski, M. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Age-related+cognitive+deficits+in+rhesus+monkeys+mirror+human+deficits+on+an+automated+test+battery.">Age-related cognitive deficits in rhesus monkeys mirror human deficits on an automated test battery.</a> Neurobiol Aging. 31 (6), 1020-1031 (2010).</li><li>Rock, P. L., Roiser, J. P., Riedel, W. J., Blackwell, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+impairment+in+depression:+a+systematic+review+and+meta-analysis.">Cognitive impairment in depression: a systematic review and meta-analysis.</a> Psychol Med. , 1-12 (2013).</li><li>Stuss, D. 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Nessun conflitto di interessi dichiarati.

I deficit di flessibilità cognitiva mediati dal PFC rappresentare un handicap significativo associato con una varietà di disturbi neurologici e neuropsichiatrici, e possono avere un impatto significativo sui risultati e la qualità della vita delle persone che soffrono di questi disturbi. Ottimizzazione della AST per l&#39;uso nei topi è di vitale importanza per indagare le basi genetiche di malattie accoppiati a prefrontali disfunzione cognitiva corticale mediata. Abbiamo trovato che il metodo sopra descritto è una...

Il set attenzionale spostamento compito (AST) è stato sviluppato come una misura di attenzione e flessibilità cognitiva in ratti oltre un decennio fa 1,2. AST è modellato il componente intradimensional / extradimensionale di Cambridge Neuropsychological prova Automated Battery (Cantab), che viene utilizzato per identificare disfunzioni cognitive negli esseri umani e primati non umani 3,4. Mentre la capacità di imparare semplici regole rimane intatto, deficit di apprendimento di modificare una risposta quando le regole sono cambiate si trovano nei pazienti affetti da una serie di disturbi neuropsichiatrici (cioè, la schizofrenia, disturbo ossessivo-compulsivo, depressione), malattie neurodegenerative (ad esempio, morbo di Parkinson) e in pazienti con lesioni alla corteccia prefrontale 5. Più in generale, questi pazienti sono descritti come aventi deficit nella flessibilità cognitiva. Deficit analoghe sono state esposte in entrambi i primati non umani e roditori quando le lesioni to la corteccia prefrontale sono stati indotti 1,6-8. Questi deficit indicano uno stato di rigidità cognitiva o una compromissione della capacità di spostare set attenzionale. Un set attentivo si forma quando un soggetto apprende che un insieme di regole può essere applicato a stimoli complessi per differenziare pertinente spunti irrilevanti. Ad esempio, nel AST, gli animali imparare a prestare attenzione e rispondere alla cue utile (cioè, media scavando) e ignorare un cue irrilevante (cioè, odore), accoppiando un premio alimentare con il mezzo. Questa associazione è poi rafforzato in attività successive in cui il tipo di scavare medie e odore cambia, ma l&#39;associazione accoppiamento tra medio e ricompensa rimane. Questa regola rinforzato forma un set cognitivo. Due tappe all&#39;interno degli aspetti misura protocollo AST di flessibilità cognitiva: inversione e il turno extra-dimensionale. Nella fase di inversione, gli stimoli precedentemente negativi all&#39;interno di una dimension (media in questo esempio) è ora positivo, che sfida l&#39;animale di ignorare gli stimoli positivi della fase precedente. Ad esempio, se a medio scavando sentito era stimoli positivi nella fase precedente e carta era stimoli negativi, ora è vero il contrario. Questa sfida flessibilità dell&#39;animale in quanto deve mantenere il set attenzionale (cioè di media è la dimensione del caso), mentre alterando la regola appresa per stimolo e coppia di ricompensa in una dimensione. La formazione di un insieme attentivo è contestata nella fase turno extra-dimensionale, quando la dimensione irrilevante (odore in questo esempio) diventa la dimensione rilevante. Una risposta perseverative, come indicato da una scelta continua utilizzando la regola precedentemente appreso, sia a fase riflette un deficit di flessibilità cognitiva. Studi lesione sia primati non umani e roditori hanno mostrato specifiche regioni della corteccia prefrontale può essere attribuito alla capacità di Perform particolari fasi della AST 1,9. Lesioni della corteccia orbitofrontale (OFC), una subregione della corteccia prefrontale (PFC), hanno dimostrato di indurre deficit di inversione di apprendimento sul AST 8. Inoltre, le lesioni alla corteccia prefrontale mediale (MPFC) portano a difficoltà specifiche di svolgimento del turno extra-dimensionale. Mentre numerosi studi che utilizzano l&#39;AST sono stati condotti su ratti e primati non umani, relativamente pochi hanno utilizzato AST come misura della funzione cognitiva nei topi. Data la facilità di manipolazione genetica nei topi, e la necessità critica per misurare la funzione della corteccia prefrontale in studio di una serie di disturbi, adattare e convalidare questa misura comportamentale nei topi è un&#39;aggiunta importante per la ricerca sulle malattie associate a disfunzione PFC. Il protocollo qui descritto è una modifica della procedura da Birrell e Brown 1, ottimizzato per applicazioni nei topi e riflette molti dei mouse specifiadattamenti c che sono stati precedentemente segnalati 2,6,10-13.

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			<td height="42" style="height:42px;width:216px;">Name of Material/ Equipment</td>
			<td style="width:227px;">Company</td>
			<td style="width:159px;">Catalog Number</td>
			<td style="width:327px;">Comments/Description</td>
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			<td height="21" style="height:21px;width:216px;">Testing Chamber</td>
			<td style="width:227px;"></td>
			<td style="width:159px;"></td>
			<td colspan="2">Fabricated in-house, specifications can be found in protocol</td>
		</tr>
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			<td height="21" style="height:21px;width:216px;"></td>
			<td style="width:227px;"></td>
			<td style="width:159px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">3 0z. Ramekins</td>
			<td style="width:227px;">BIA Cordon Bleu</td>
			<td style="width:159px;">900002S12</td>
			<td>Purchased on amazon.com</td>
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			<td height="21" style="height:21px;width:216px;">Essential Oils:</td>
			<td style="width:227px;">Fronteir Natural Products Co-Op</td>
			<td style="width:159px;"></td>
			<td colspan="2">Purchased on http://www.frontiercoop.com/prodlist.php?ct=anpceoeo</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Clove Bud</td>
			<td style="width:227px;"></td>
			<td align="right">191114</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Red Thyme</td>
			<td style="width:227px;"></td>
			<td align="right">191140</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Lemon</td>
			<td style="width:227px;"></td>
			<td align="right">190810</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Cinnamon Leaf</td>
			<td style="width:227px;"></td>
			<td align="right">191111</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Rosemary</td>
			<td style="width:227px;"></td>
			<td align="right">191133</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Citronella Java</td>
			<td style="width:227px;"></td>
			<td align="right">191112</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Vanilla in jojoba oil</td>
			<td style="width:227px;"></td>
			<td align="right">191231</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Anise Seed</td>
			<td style="width:227px;"></td>
			<td align="right">191102</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Ginger</td>
			<td style="width:227px;"></td>
			<td align="right">191121</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Nutmeg</td>
			<td style="width:227px;"></td>
			<td align="right">191161</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;"></td>
			<td style="width:227px;"></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Filter Paper, 9.0 cm diameter</td>
			<td style="width:227px;">VWR International</td>
			<td>28310-048</td>
			<td>Purchased on https://us.vwr.com/</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;"></td>
			<td style="width:227px;"></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Digging Media</td>
			<td style="width:227px;"></td>
			<td style="width:159px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Raffia</td>
			<td>Ashland 8 oz Raffia</td>
			<td style="width:159px;">n/a</td>
			<td>Purchased on http://www.michaels.com/ 
			Cut into 1/2&#34; to 1&#34; strips</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Green Felt</td>
			<td>Creatology Basic Felt Forest/Dark Green 36 in x 36 in&#160;</td>
			<td style="width:159px;">n/a</td>
			<td>Purchased on http://www.michaels.com/ 
			cut into 1 cm x 1 cm squares</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Brown foam</td>
			<td>Creatology Fun Foam 18 x 12 in sheets (light brown/tan)</td>
			<td style="width:159px;">n/a</td>
			<td>Purchased on http://www.michaels.com/ 
			cut into 1/2 cm x 2 cm rectangles</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Crepe paper (yellow)</td>
			<td>Celebrate It Paper Crinkle 4 oz yellow jumbo</td>
			<td style="width:159px;">n/a</td>
			<td>Purchased on http://www.michaels.com/ 
			Cut into 1/2&#34; to 1&#34; strips</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Ribbon (turqoise)</td>
			<td>Celebrate It Wide Ribbon 4 in x 10 yd 100% polyester&#160;</td>
			<td style="width:159px;">n/a</td>
			<td>Purchased on http://www.michaels.com/ 
			cut into 1 cm x 1 cm squares</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Metallic&#160;</td>
			<td>Celebrate It Metallic Crinkle Gold 2 oz</td>
			<td style="width:159px;">n/a</td>
			<td>Purchased on http://www.michaels.com/ 
			Cut into 1/2&#34; to 1&#34; strips</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Googly Eyes, 4 mm</td>
			<td style="width:227px;"></td>
			<td>ME4144</td>
			<td colspan="2">Purchased on http://factorydirectcraft.com/index.php</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Black Sequins, 3 mm</td>
			<td style="width:227px;"></td>
			<td>8780BK</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Pink Pom Poms, 1/4 inch</td>
			<td style="width:227px;"></td>
			<td style="width:159px;">1018221</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Pipe Cleaners, red</td>
			<td style="width:227px;"></td>
			<td style="width:159px;">108430</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Bedding material/sawdust</td>
			<td style="width:227px;"></td>
			<td style="width:159px;"></td>
			<td>Obtained from in-house animal resources</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;"></td>
			<td style="width:227px;"></td>
			<td style="width:159px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Timer</td>
			<td style="width:227px;">Control Company</td>
			<td align="right" style="width:159px;">5000</td>
			<td colspan="2">Purchased on http://www.control3.com/5000p.htm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;"></td>
			<td style="width:227px;"></td>
			<td style="width:159px;"></td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Lightly sweetened dry breakfast cereal loops</td>
			<td style="width:227px;">HEB&#160;</td>
			<td style="width:159px;"></td>
			<td colspan="2">Honey nut toasted oats used in the protocol described, any lightly sweet coated breakfast cereal is recommended</td>
		</tr>
	</tbody>
</table>

the attentional set shifting task: a measure of cognitive flexibility in mice

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many neuropsychiatric and neurodevelopmental disorders, including depression, post-traumatic stress disorder, schizophrenia and autism spectrum disorder. Deficits in cognitive function also represent the most difficult symptom domain&#160;to successfully treat, as serotonin reuptake inhibitors and tricyclic antidepressants have only modest effects. Functional neuroimaging studies and postmortem analysis of human brain tissue implicate the PFC as being a primary region of dysregulation in patients with these disorders. However, preclinical behavioral assays used to assess these deficits in mouse models which can be readily manipulated genetically and could provide the basis for studies of new treatment avenues have been underutilized. Here we describe the adaptation of a behavioral assay, the attentional set shifting task (AST), to be performed in mice to assess prefrontal cortex mediated cognitive deficits. The neural circuits underlying behavior during the AST are highly conserved across humans, nonhuman primates and rodents, providing excellent face, construct and predictive validity.

La misura dipendente tipico in questa prova è il numero di prove per ogni fase per soddisfare il criterio (o 8 corrette scelte consecutive). La figura 4A mostra il numero medio di prove per soddisfare il criterio in ogni fase trattata C57BL / 6J utilizzando la AST. Come topi formano un insieme attentivo sulla dimensione cue rilevante (odore o media), prestazioni miglioreranno, come indicato da una riduzione in studi per soddisfare criteri in turni intradimensional successive, e le fasi di inversione e ...

Watch this Scientific Journal Video about The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice at JoVE.com

The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice

L&#39;obiettivo di questo protocollo è quello di effettuare un test comportamentale, come il set attenzionale spostamento compito (AST) per valutare prefrontale flessibilità cognitiva cortex-mediata nei topi.

La Task attenzionale Set Shifting: una certa flessibilità cognitiva nei topi

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many ...

the-attentional-set-shifting-task-measure-cognitive-flexibility

Research

JoVE Journal

Behavior

27.0K Views.  University of Texas Health Science Center at San Antonio.  L'obiettivo di questo protocollo è quello di effettuare un test comportamentale, come il set attenzionale spostamento compito (AST) per valutare prefrontale flessibilità cognitiva cortex-mediata nei topi. 

Video: The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice

The Crossmodal Congruency Task as a Means to Obtain an Objective Behavioral Measure in the Rubber Hand Illusion Paradigm

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden hand is touched. If the viewed and felt touches are given at the same time then this is sufficient to induce the compelling experience that the rubber hand is one's own hand. The RHI can be used to investigate exactly how the brain constructs distinct body representations for one's own body. Such representations are crucial for successful interactions with the external world. To obtain a subjective measure of the RHI, researchers typically ask participants to rate statements such as "I felt as if the rubber hand were my hand". Here we demonstrate how the crossmodal congruency task can be used to obtain an objective behavioral measure within this paradigm.
The variant of the crossmodal congruency task we employ involves the presentation of tactile targets and visual distractors. Targets and distractors are spatially congruent (i.e. same finger) on some trials and incongruent (i.e. different finger) on others. The difference in performance between incongruent and congruent trials - the crossmodal congruency effect (CCE) - indexes multisensory interactions. Importantly, the CCE is modulated both by viewing a hand as well as the synchrony of viewed and felt touch which are both crucial factors for the RHI.
The use of the crossmodal congruency task within the RHI paradigm has several advantages. It is a simple behavioral measure which can be repeated many times and which can be obtained during the illusion while participants view the artificial hand. Furthermore, this measure is not susceptible to observer and experimenter biases. The combination of the RHI paradigm with the crossmodal congruency task allows in particular for the investigation of multisensory processes which are critical for modulations of body representations as in the RHI.

We demonstrate how an objective measure can be employed in the widely employed rubber hand illusion paradigm. This measure is obtained by modifying the well-established crossmodal congruency task. This task allows the investigation of multisensory processes which are critical for modulations of body representations as in the rubber hand illusion.

La Task Congruenza crossmodali come un mezzo per ottenere una misura comportamentale Obiettivo della mano di gomma Illusion Paradigma

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden ...

Ricerca

Comportamento

A Dual Task Procedure Combined with Rapid Serial Visual Presentation to Test Attentional Blink for Nontargets

When viewers search for targets in a rapid serial visual presentation (RSVP) stream, if two targets are presented within about 500 msec of each other, the first target may be easy to spot but the second is likely to be missed. This phenomenon of attentional blink (AB) has been widely studied to probe the temporal capacity of attention for detecting visual targets. However, with the typical procedure of AB experiments, it is not possible to examine how the processing of non-target items in RSVP may be affected by attention. This paper describes a novel dual task procedure combined with RSVP to test effects of AB for nontargets at varied stimulus onset asynchronies (SOAs). In an exemplar experiment, a target category was first displayed, followed by a sequence of 8 nouns. If one of the nouns belonged to the target category, participants would respond &#8216;yes&#8217; at the end of the sequence, otherwise participants would respond &#8216;no&#8217;. Two 2-alternative forced choice memory tasks followed the response to determine if participants remembered the words immediately before or after the target, as well as a random word from another part of the sequence. In a second exemplar experiment, the same design was used, except that 1) the memory task was counterbalanced into two groups with SOAs of either 120 or 240 msec and 2) three memory tasks followed the sequence and tested remembrance for nontarget nouns in the sequence that could be anywhere from 3 items prior the target noun position to 3 items following the target noun position. Representative results from a previously published study demonstrate that our procedure can be used to examine divergent effects of attention that not only enhance targets but also suppress nontargets. Here we show results from a representative participant that replicated the previous finding.&#160;

This paper describes a novel dual task procedure combined with Rapid Serial Visual Presentation to look at attentional blink at varied stimulus onset asynchronies. This experimental procedure differed from others in that it tested attentional blink for nontargets.

Una procedura di duplice compito Combinato con Rapid Serial presentazione visiva a Test attenzionale Blink per Nontargets

When viewers search for targets in a rapid serial visual presentation (RSVP) stream, if two targets are presented within about 500 msec of each other, the ...

An Operant Intra-/Extra-dimensional Set-shift Task for Mice

Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric diseases. The most widely used neuropsychological tests for the evaluation of attentional set-shifting in human subjects are the Wisconsin Card Sorting Test (WCST) and the CANTAB Intra-/Extra-dimensional set shift task (ID/ED). These tasks have proven clinical relevance and have been modified and successfully adapted for research in animal models. However, currently available tasks for rodents present several limitations, mainly due to their manual-based testing procedures, which are hampering translational advances in psychiatric medicine. To overcome these limitations and to better mimic the original version in primates, we present the development of a novel operant-based two-chamber ID/ED "Operon" task for rodents. We demonstrated the effectiveness of this novel task to measure different facets of cognitive flexibility in mice including attentional set formation and shifting, and reversal learning. Moreover, we show the high flexibility of this task in which three different perceptual dimensions can be manipulated with a high number of stimuli cues for each dimension. This novel ID/ED Operon task can be an effective preclinical tool for drug testing and/or large genetic screening relevant to the study of executive dysfunction and cognitive symptoms found in psychiatric disorders.

Attentional set-shifting cognitive abnormalities are a core feature of many psychiatric diseases. Here, we present the development of a novel automatic system for the effective study of attentional set-shifting abilities, executive functions and other cognitive abilities in mice with high translational validity to human studies.

Un operante intra / extra-dimensionale Set-shift attività per Mice

Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric ...

The Emotional Stroop Task: Assessing Cognitive Performance under Exposure to Emotional Content

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The difference shows that people are affected by the emotional content conveyed by the carrier words even though they are irrelevant to the color-naming task at hand. The ESE has been widely deployed with patient populations, as well as with non-selected populations, because the emotion words can be selected to match the tested pathology. The ESE is a powerful tool, yet it is vulnerable to various threats to its validity. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them. The most prevalent threat to the validity of existing ESE studies is sustained effects and habituation wrought about by repeated exposure to emotion stimuli. Consequently, the order of exposure to emotion and neutral stimuli is of utmost importance. We show that in the standard design, only one specific order produces the ESE.

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than those of neutral words. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them.

La emotivo Stroop Task: Valutare la performance cognitiva in esposizione al contenuto emotivo

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The ...

The Deese-Roediger-McDermott (DRM) Task: A Simple Cognitive Paradigm to Investigate False Memories in the Laboratory

The Deese,&#160;Roediger and McDermott&#160;(DRM) task is a false memory paradigm in which subjects are presented with lists of semantically related words (e.g., nurse, hospital, etc.) at encoding. After a delay, subjects are asked to recall or recognize these words. In the recognition memory version of the task, subjects are asked whether they remember previously presented words, as well as related (but never presented) critical lure words (&#39;doctor&#39;). Typically, the critical word is recognized with high probability and confidence. This false memory effect has been robustly demonstrated across short (e.g., immediate, 20 min) and long (e.g., 1, 7, 60 d) delays between encoding and memory testing. A strength of using this task to study false memory is its simplicity and short duration. If encoding and retrieval components of the task occur in the same session, the entire task can take as little as 2 - 30 min. However, although the DRM task is widely considered a &#39;false memory&#39; paradigm, some researchers consider DRM illusions to be based on the activation of semantic memory networks in the brain, and argue that such semantic gist-based false memory errors may actually be useful in some scenarios (e.g., remembering the forest for the trees; remembering that a word list was about &#34;doctors&#34;, even though the actual word &#34;doctor&#34; was never presented for study). Remembering the gist of experience (instead of or along with individual details) is arguably an adaptive process and this task has provided a great deal of knowledge about the constructive, adaptive nature of memory. Therefore, researchers should use caution when discussing the overall reach and implications of their experiments when using this task to study &#39;false memory&#39;, as DRM memory errors may not adequately reflect false memories in the real world, such as false memory in eyewitness testimony, or false memories of sexual abuse.

The Deese-Roediger-McDermott DRM Task: A Simple Cognitive Paradigm to Investigate False Memories in the Laboratory

Here we present the Deese,&#160;Roediger and McDermott&#160;(DRM) task, a tool to study false memories in the laboratory. Subjects study lists of semantically related words (e.g.,&#160;nurse, sick, etc.), and later falsely remember an unstudied word (doctor) that represents the gist, or theme, of the word list.

Il Deese-Roediger-McDermott (DRM) Compito: Un semplice paradigma cognitivo per Indagare falsi ricordi in laboratorio

The Deese,&#160;Roediger and McDermott&#160;(DRM) task is a false memory paradigm in which subjects are presented with lists of semantically related words ...

New Variations for Strategy Set-shifting in the Rat

Behavioral flexibility is crucial for survival in changing environments. Broadly defined, behavioral flexibility requires a shift of behavioral strategy based on a change in governing rules. We describe a strategy set-shifting task that requires an attentional shift from one stimulus dimension to another. The paradigm is often used for testing cognitive flexibility in primates. However, the rodent version has not been as extensively developed. We have recently extended an established set-shifting task in the rat1 by requiring attention to different stimuli according to context. All the experimental conditions required animals to choose either a left or right lever. Initially, all animals had to choose on the basis of the location of the lever. Subsequently, a change in the rule occurred, which required a shift in set from location-based rule to a rule in which the correct lever was indicated by a light cue. We compared performance on three different versions of the task, in which the light stimulus was either novel, previously relevant, or previously irrelevant. We found that specific neurochemical lesions selectively impaired the ability to make particular types of set shift as measured by the performance on the different versions of the task.

Set-shifting, a form of behavioral flexibility, requires an attentional shift from one stimulus dimension to another. We extended an established rodent set-shifting task1 by requiring attention to different stimuli according to context. The task was combined with specific lesions to identify neuron subtypes underlying a successful shift.

Nuove Variazioni per strategia Set-shifting nel ratto

Behavioral flexibility is crucial for survival in changing environments. Broadly defined, behavioral flexibility requires a shift of behavioral strategy ...

Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice

Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous research determined a profound impact of gentle handling protocols on the well-being of laboratory mice. By introducing clicker training to the keeping of mice, not only do we promote the amicable treatment of mice, but we also enable them to experience cognitive enrichment. Clicker training is a form of positive reinforcement training using a conditioned secondary reinforcer, the "click" sound of a clicker, which serves as a time bridge between the strengthened behavior and an upcoming reward. The effective implementation of the clicker training protocol with a cohort of 12 BALB/c inbred mice of each sex proved to be uncomplicated. The mice learned rather quickly when challenged with tasks of the clicker training protocol, and almost all trained mice overcame the challenges they were given (100% of female mice and 83% of male mice). This study has identified that clicker training for mice strongly correlates with reduced fear in the mice during human-mice interactions, as shown by reduced anxiety-related behaviors (e.g., defecation, vocalization, and urination) and fewer depression-like behaviors (e.g., floating). By developing a reliable protocol that can be easily integrated into the daily routine of the keeping of laboratory mice, the lifetime experience of welfare in the mice can be improved substantially.

The development of new refinement strategies for laboratory mice is a challenging task that contributes towards fulfilling the 3R principle. This protocol introduces clicker training as a cognitive enrichment program for laboratory mice.

L&#39;introduzione di Clicker Training come un arricchimento conoscitivo per topi di laboratorio

Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous ...

The "Motor" in Implicit Motor Sequence Learning: A Foot-stepping Serial Reaction Time Task

This protocol describes a modified serial reaction time (SRT) task used to study implicit motor sequence learning. Unlike the classic SRT task that involves finger-pressing movements while sitting, the modified SRT task requires participants to step with both feet while maintaining a standing posture. This stepping task necessitates whole body actions that impose postural challenges. The foot-stepping task complements the classic SRT task in several ways. The foot-stepping SRT task is a better proxy for the daily activities that require ongoing postural control, and thus may help us better understand sequence learning in real-life situations. In addition, response time serves as an indicator of sequence learning in the classic SRT task, but it is unclear whether response time, reaction time (RT) representing mental process, or movement time (MT) reflecting the movement itself, is a key player in motor sequence learning. The foot-stepping SRT task allows researchers to disentangle response time into RT and MT, which may clarify how motor planning and movement execution are involved in sequence learning. Lastly, postural control and cognition are interactively related, but little is known about how postural control interacts with learning motor sequences. With a motion capture system, the movement of the whole body (e.g., the center of mass (COM)) can be recorded. Such measures allow us to reveal the dynamic processes underlying discrete responses measured by RT and MT, and may aid in elucidating the relationship between postural control and the explicit and implicit processes involved in sequence learning. Details of the experimental set-up, procedure, and data processing are described. The representative data are adopted from one of our previous studies. Results are related to response time, RT, and MT, as well as the relationship between the anticipatory postural response and the explicit processes involved in implicit motor sequence learning.

The &quot;Motor&quot; in Implicit Motor Sequence Learning: A Foot-stepping Serial Reaction Time Task

We introduce the foot-stepping serial reaction time (SRT) task. This modified SRT task, complementing the classic SRT task that involves only finger-pressing movement, better approximates daily sequenced activities and allows researchers to study the dynamic processes underlying discrete response measures and disentangle the explicit process operating in implicit sequence learning.

Il "motore" a motore implicito sequenza di apprendimento: una reazione seriale un passo piede volta compito

This protocol describes a modified serial reaction time (SRT) task used to study implicit motor sequence learning. Unlike the classic SRT task that ...

Eye Tracking During Visually Situated Language Comprehension: Flexibility and Limitations in Uncovering Visual Context Effects

The present work is a description and an assessment of a methodology designed to quantify different aspects of the interaction between language processing and the perception of the visual world. The recording of eye-gaze patterns has provided good evidence for the contribution of both the visual context and linguistic/world knowledge to language comprehension. Initial research assessed object-context effects to test&#160;theories of modularity in language processing. In the introduction, we describe how subsequent investigations have taken the role of the wider visual context in language processing as a research topic in its own right, asking questions such as how our visual perception of events and of speakers contributes to&#160;comprehension informed by&#160;comprehenders&#39; experience. Among the examined aspects of the visual context are actions, events, a speaker&#39;s gaze, and emotional facial expressions, as well as spatial object configurations. Following an overview of the eye-tracking method and its different applications, we list the key steps of the methodology in the protocol, illustrating how to successfully use it to study visually-situated language comprehension. A final section presents three sets of representative results and illustrates the benefits and limitations of eye tracking for investigating the interplay between the perception of the visual world and language comprehension.

The present article reviews an eye-tracking methodology for studies on language comprehension. To obtain reliable data, key steps of the protocol must be followed. Among these are the correct set-up of the eye tracker (e.g., ensuring good quality of the eye and head images) and accurate calibration.

Eye Tracking durante la comprensione del linguaggio visivo situato: Flessibilità e limitazioni a scoprire gli effetti di contesto visivo

The present work is a description and an assessment of a methodology designed to quantify different aspects of the interaction between language processing ...

Using Rapid Serial Visual Presentation to Measure Set-Specific Capture, a Consequence of Distraction While Multitasking

This method uses a rapid serial visual presentation (RSVP) paradigm to measure the cost of distraction when participants maintain multiple search goals. The protocol identifies two types of distraction within a single task - contingent attentional capture and set-specific capture - that represent different types of limitations of cognitive processing. Participants search for letters in two or more &#34;target&#34; ink colors (e.g., green and orange) within a continuous RSVP stream of heterogeneously colored letters, while ignoring two peripheral RSVPs of letters. Upon detecting a target, participants are to identify the letter. On some trials, target-colored distractors appear in the periphery just prior to the presentation of a target, causing a drop in target identification performance. Contingent attentional capture is observed by examining performance on trials in which the peripheral distractor is the same color as the target on that trial (e.g., both orange). Set-specific capture is represented by performance on trials in which the peripheral distractor is target-colored (e.g., orange), but not the same color as the target on that trial (e.g., green.) By varying the amount of time (i.e., the number of stimuli appearing) between the presentation of the distractor and the target, researchers can observe how participants recover from these distraction costs over time. As compared to static displays that are often used to measure contingent attentional capture, the dynamic display produces much larger effects, allowing the researcher to identify subtle effects of smaller manipulations. An unusual aspect of our design is that it employs a continuous display; &#34;filler&#34; stimuli connect one trial to the next seamlessly, and participants respond during this interval whenever they detect a target. The continuous display reduces chance performance to near-zero levels (rather than 50%) and provides researchers with a more sensitive measure of performance differences across trial types.

This method uses a dynamic visual display to index costs of distraction during visual search, including both &#34;contingent attentional capture&#34; and &#34;set-specific capture,&#34; which is a cost of distraction that occurs when the participants maintain multiple search goals simultaneously. This method has revealed basic mechanisms and limitations of visual attention.

Utilizzando rapida presentazione visiva seriale per misurare specifici Set Capture, una conseguenza della distrazione mentre Multitasking

This method uses a rapid serial visual presentation (RSVP) paradigm to measure the cost of distraction when participants maintain multiple search goals. ...