Esta pesquisa foi apoiada por doações R01-MH090127, P30-MH089868 do Instituto Nacional de Saúde Mental e número prêmio UL1TR001120 do Centro Nacional para a Promoção da Ciência Translacional. O conteúdo é da exclusiva responsabilidade dos autores e não representam necessariamente a posição oficial do NIMH ou NCATS. Além disso, gostaríamos de reconhecer com gratidão Dr. David Morilak por sua valiosa experiência para orientar o desenvolvimento do método cedo.

NOTA: Os animais utilizados neste estudo são do sexo masculino camundongos C57BL / 6J entre 4 e 6 meses de idade, para os melhores resultados. Ratos são mantidos em um ciclo de luz inverso, a fim de testá-los convenientemente durante a fase ativa (escuro). Se o comportamento é realizado em uma sala separada da carcaça, os ratos são permitidos pelo menos 1 hora para se aclimatar seguinte transporte para a sala de ensaios. Teste comportamental é realizado sob condições de luz vermelha minimizar a perturbação da actividade normal dos ratos tão pouco quanto possível, enquanto ainda permitindo que o experimentador iluminação adequada para acompanhar visualmente a sessão de testes. NOTA: Todos os aspectos do procedimento experimental aqui descritos foram realizados de acordo com o Guia para o Cuidado e Uso de Animais de Laboratório, 8ª (NRC) e foram aprovados pelo Comitê de Uso e Cuidado Animal Institucional na Universidade do Texas em Ciências da Saúde Center em San Antonio. <ol><li> Encha forminhas de cerâmica (não-poroso; 1.5 &quot;profundidade x 2,5 cm de diâmetro), a borda interna com cavando meio (aproximadamente 1&quot; a partir de baixo); rodadas de papel filtro de corte ao meio e colado dentro de trás do ramekin (Figura 1A) </li><li> Quebre levemente adoçado cereal seco pequeno-almoço (recompensa alimentar) - Nut mel ou variedades de açúcar revestido, em cerca de 20 peças mg para as fases de aclimatação, treinamento e teste. </li><li> Faça um conjunto de atenção transferência de tarefas (AST) câmara (Figura 1B): Aclimatar treinar e testar cada rato em câmaras individuais; recomendam produção de pelo menos 8 câmaras. <ol><li> Construa uma câmara AST 12 &quot;x 8&quot; x 7 &quot;; muros e portão início feitas de acrílico branco opaco que é fácil de limpar com etanol 70%. O estilo guilhotina, removível portão de partida separa câmara em uma área de espera (5 &quot;x 8&quot;) e área de testes (7 &quot;x 8&quot;). </li><li> Incluir um claro 5221; x7 &quot;divisória amovível que separa os dois lados da área de testes de maneira uniforme; cortar três ¼ &quot;buracos de diâmetro na parte inferior da divisória para permitir o acesso cheirar, espaçadas 1&quot; distante e 1 &quot;a partir da frente da partição (Figura 1C). </li></ol></li></ol> 2. Visão geral do procedimento (Figura 2) <ol><li> Antes da AST, ratos de casa individualmente e permitir-lhes para se ajustar a um ciclo de luz reversa para, pelo menos, uma semana. </li><li> Aclimatar, treinar e testar cada animal em câmaras de teste individuais. Atribuir cada câmara a um mouse e limpo com etanol a 70% depois de terminar o último dia de testes. Isso irá minimizar o estresse durante os testes, fazendo o cheiro câmara como &quot;casa-gaiola&quot; ou &quot;self&quot;. </li><li> Perfume os vasos de ensaio 2 dias antes do teste para permitir o perfume para dissipar; camundongos não vai cavar em vasos que têm um odor muito forte. Usando uma seringa com uma agulha de 25 G, adicionar cerca de 0,1 ml deóleo essencial para a parte superior do papel de filtro. </li></ol> 3. Manutenção (Dias 1-8) <ol><li> Lidar com ratos a partir de 8 dias antes do primeiro dia de restrição alimentar. Isso irá reduzir o estresse associado com a manipulação durante o teste. </li><li> Pesar e pesos corporais registro a cada dia de manuseio. Lidar com cada rato 2-3 min por dia. </li><li> Se vários experimentadores devem ser envolvidos em testar um conjunto de ratos, garantir que cada pesquisador participa do processo de manipulação para aumentar a familiaridade com os experimentadores e reduzir o estresse e ansiedade experientes no treinamento ou dias de testes. </li><li> Continuar manuseamento e pesos de gravação ao longo da duração dos testes. </li></ol> 4. A restrição alimentar (Dias 12/09) <ol><li> Começando 4 dias antes do início da aclimatação, os ratos no lugar de uma dieta restrita para manter os ratos a 80-85% do seu peso corporal alimentar livre. Dê um grama de alimento por rato por dia. Se o peso do corpo cai abaixodo intervalo especificado dar 2 gramas por dia até que eles voltem para o intervalo apropriado. </li><li> Coloque 2 ramequins na frente de cada gaiola, a fim de permitir que os ratos se aclimatar para os vasos de teste. Estes são os mesmos pontos usados ​​para treinar o mouse para cavar para uma recompensa alimentar. </li><li> Adicionar 2 gramas de comida e uma peça de recompensa alimentar (metade de um pedaço de cereal em cada) em ramekins cada dia durante 4 dias. </li><li> Se o comportamento está a ser realizado numa sala separada do que aquela em que os ratos são alojados, começando no dia 1 de restrição alimentar, os ratinhos de transporte para a sala de teste durante pelo menos 1 hr por dia antes de voltar para a sala de alojamento para permitir eles se adapte à sala de ensaios. </li><li> No último dia de restrição alimentar, antes do início da aclimatação, mudar a cama gaiola de origem. A roupa de cama gaiola não será alterado novamente até após a conclusão do teste para reduzir o estresse ou ansiedade experimentada durante o treinamento e teste (menos que seja absolutamente necessário). </li><li> Manterem ratinhos restrição alimentar até ao final do teste. Nos dias 13-17, dar comida camundongos após aclimatação, treinamento ou de teste com base em uma estimativa da quantidade de alimentos consumidos recompensa (geralmente &lt;1g de pellet de alimentos). </li></ol> 5. Aclimatação (Dias 13-14) <ol><li> Começando 2 dias antes do início da formação, realizar aclimatação durante o ciclo escuro com luz vermelha. </li><li> Espalhe uma pequena quantidade de roupas de cama suja da gaiola na câmara, isso vai reduzir o estresse de estar em um novo ambiente através da introdução de um familiar &quot;home-gaiola&quot; ou &quot;self&quot; cheiro para a câmara de teste (a mesma câmara será usado para um único rato para a duração do treinamento e teste). </li><li> Coloque um ramekin limpo com água na sala de espera da câmara; camundongos tendem a não comer, se eles não têm acesso à água. </li><li> Coloque os dois ramequins que têm sido utilizados para a restrição alimentar na área de testes com uma recompensa de alimentos (~ 20pedaço de cereais mg) em cada. </li><li> Posicione o mouse na área de espera; remover a porta de início e permitir que o rato explorar a câmara durante 1 h. </li><li> Continuamente adicionar recompensas alimentares (~ peça cereal 20 mg) para os ramequins vazias a fim de incentivar os ratos para explorar a área de testes e as panelas com freqüência. </li><li> Certifique-se de que o rato pode ver o experimentador durante todo o período de aclimatação de modo que a presença do experimentador não é um estressor adicional durante o teste. </li></ol> 6. Treinamento (Dia 15) <ol><li> Posicione o mouse na área de espera. </li><li> Coloque as forminhas vazias, cada uma contendo uma recompensa alimentar (~ peça cereal 20 mg), para a área de testes e levantar o portão de partida. Permitir mouse de 3 min para recuperar as recompensas alimentares. Repita este passo várias vezes. </li><li> Aos poucos, adicione serragem / rato cama gaiola para as panelas em ensaios subseqüentes. Permitir que o mouse 3 min para recuperar a recompensa alimentar de cada pote antes de terminar o triai. Uma vez que o rato tenha recuperado a recompensa alimentar de cada pote, passe para a próxima prova. Se o mouse não faz tentativas de cavar uma vez que a recompensa alimentar é parcialmente coberto, pode ser fornecido dicas (ou seja, polvilhe pó cereal sobre a área da recompensa alimentar, fazer um recuo na serragem sobre a área de recompensa alimentar, descobrir parte do recompensa alimentar). </li><li> Continue adicionando serragem / roupa de cama depois de cada julgamento até que a recompensa alimentar é totalmente coberto e o mouse demonstra de forma confiável a capacidade de escavar em um pote cheio de encontrar a recompensa alimentar. </li><li> Se um rato não demonstrou de forma confiável a capacidade de encontrar uma recompensa comida em um pote cheio dentro de 2 horas do início da formação, continuam a um segundo dia de treinamento. Manter o mouse sobre a restrição alimentar e repita este procedimento no dia seguinte. </li><li> Se o mouse não consegue cavar para uma recompensa alimentar depois de dois dias sucessivos, excluí-lo do restante do experimento, e anotar como um &quot;não conseguiu cavar&quot; no expregistro erimental. </li></ol> 7. Testes (Dias 16-17): <ol><li> Em um dia, testar discriminação simples (SD), a discriminação composto (CD), a reversão (R1), e mudança intra-dimensional (IDS). </li><li> No segundo dia, testar a mudança intra-dimensional 2 (IDS2), shift intra-dimensional 3 (IDS3), a reversão 2 (R2; opcional), shift extra-dimensional (EDS). </li><li> Meios par e aromas, como mostrado na Tabela 1. </li><li> Na hora de lidar no dia de testes, camundongos dar uma recompensa alimentar para evitar a falta de foco durante os testes devido à fome. A partir deste ponto até ao final do dia de teste, não fornecem qualquer alimento excepto recompensas para escolhas correctas. </li><li> No início do ensaio, usando uma pinça (limita a propagação de cheiros entre potes), colocar um pedaço do alimento de recompensa no pote que indica uma escolha correcta. A recompensa de alimentos deve ser totalmente coberto pela mídia (ver Figura 3). Para evitar uma sugestão perfume da recompensa alimentar, polvilhe o cereal poeiraVER todas as panelas no início do estágio. </li><li> Posicione o mouse na área de espera com o portão fechado início. Colocar os vasos de ambos os lados da câmara de teste. O teste inicia-se quando a porta de início é removido e o temporizador é iniciado. Permitir que cada rato 3 min por tentativa de fazer uma escolha. Grave a escolha (correta ou incorreta) e tempo até o rato fez uma escolha para cada ensaio. NOTA: A &quot;escolha&quot; é indicado por uma tentativa de cavar em qualquer pote. A escavação só é registrado como uma escolha se o rato tem deslocado a mídia e cutucou seu nariz longe o suficiente no espaço ele cria para encontrar a recompensa alimentar ou o suficiente deslocadas da mídia para descobrir a recompensa alimentar. Se um rato não fez uma escolha dentro de 3 min, esta é registrada como outra opção (incorreta). </li><li> Uma vez que uma escolha foi feita para qualquer vaso, remover o pote que não foi escolhido a partir da câmara de teste. Se a escolha correta foi feita, permitir que o mouse para terminar a recompensa alimentar, antes de colocar o mouse de volta emárea de espera. Se uma escolha incorreta é feito, deixe o mouse para explorar o pote para mostrar que não há recompensa alimentar para essa escolha antes de retornar o mouse para a área de espera. </li><li> No final de cada ensaio, colocar o rato para trás na área de espera e substituir a porta de início. </li><li> Certifique-se de que o mouse se encontra com o critério de 8 ensaios corretos consecutivamente para avançar para a próxima fase da AST. Se um rato não obtenha 8 escolhas corretas consecutivas no período de 50 ensaios, ele falha nessa fase e não pode seguir em frente para completar o teste. 6 consecutivos sem escolhas (3 minutos, sem uma escolha) é um fracasso para participar e proíbe o mouse se mova para a próxima fase. </li></ol>

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Déficits na flexibilidade cognitiva mediadas pelo PFC representar uma deficiência significativa associada a uma variedade de doenças neurológicas e neuropsiquiátricas, e pode ter um grande impacto sobre os resultados e qualidade de vida dos indivíduos que sofrem desses transtornos. Otimização da AST para uso em camundongos é vital para investigar as bases genéticas de doenças acoplados a pré-frontais disfunção cognitiva mediada cortical. Verificou-se que o método descrito acima é uma medida de confiança...

O conjunto atencional transferência de tarefas (AST) foi desenvolvido como uma medida de atenção e flexibilidade cognitiva em ratos mais de uma década atrás, 1,2. AST é modelado a partir do componente intradimensional / extra-dimensional da Cambridge neuropsicológica Teste Automático de bateria (Cantab), que é usada para identificar a disfunção cognitiva em seres humanos e primatas não-humanos 3,4. Embora a capacidade de aprender regras simples permanece intacta, défices de aprendizagem para modificar uma resposta quando as regras mudaram são encontrados em pacientes que sofrem de uma variedade de distúrbios neuropsiquiátricos (por exemplo, esquizofrenia, distúrbio obsessivo compulsivo, depressão), desordens neurodegenerativas (por exemplo, A doença de Parkinson) e em pacientes com lesões no córtex pré-frontal 5. Mais geralmente, estes pacientes são descritos como tendo os défices cognitivos na flexibilidade. Défices análogos têm sido mostrados em ambos os primatas não-humanos e roedores quando as lesões to córtex pré-frontal foram induzidas 1,6-8. Estes déficits indicar um estado de inflexibilidade cognitiva ou uma capacidade prejudicada de mudar set atencional. Um conjunto de atenção é formado quando um sujeito descobre que um conjunto de regras podem ser aplicadas a estímulos complexos, a fim de diferenciar relevante a partir de pistas irrelevantes. Por exemplo, na AST, os animais vão aprender a prestar atenção e responder à sugestão relevante (ou seja, cavando médio) e ignorar uma sugestão irrelevante (ou seja, odor), emparelhando uma recompensa alimentar com o meio. Esta associação é então reforçado em tarefas subsequentes, onde o tipo de escavação de médio e odor mudanças, mas a associação emparelhado entre médio e recompensa permanece. Esta regra reforçada forma um conjunto cognitivo. Dois estágios dentro dos aspectos medida protocolo AST de flexibilidade cognitiva: reversão ea mudança extra-dimensional. Na fase de inversão, os estímulos previamente negativos no prazo de um dimension (médio, neste exemplo) agora é positivo, o que desafia o animal a ignorar os estímulos positivos a partir da etapa anterior. Por exemplo, se sentiu meio de escavação foram os estímulos positivos na fase anterior e papel foram os estímulos negativos, agora o inverso é verdadeiro. Isso desafia a flexibilidade do animal em que a Europa deve manter o conjunto de atenção (ou seja, o meio é a dimensão relevante), alterando a regra aprendida para estímulo e recompensa par dentro de uma dimensão. A formação de um conjunto de atenção é contestada na fase de mudança extra-dimensional, quando a dimensão irrelevante (odor, neste exemplo) torna-se a dimensão relevante. Uma resposta perseverativo, como indicado por uma escolha contínuo usando a regra previamente aprendido, em qualquer fase reflecte um défice cognitivo em flexibilidade. Estudos de lesões em ambos os primatas não-humanos e roedores mostraram regiões específicas do córtex pré-frontal pode ser atribuído à capacidade de perform estágios particulares do AST 1,9. Lesões no córtex orbitofrontal (OFC), uma sub-região do córtex pré-frontal (PFC), foram mostrados para induzir déficits de aprendizado reverso na AST 8. Além disso, lesões no córtex pré-frontal (MPFC) chumbo medial a dificuldades específicas na realização da mudança extra-dimensional. Enquanto numerosos estudos utilizando a AST foram realizados em ratos e primatas não-humanos, relativamente poucos têm utilizado AST como uma medida da função cognitiva em ratos. Dada a facilidade de manipulação genética em ratos, e a necessidade crítica para medir a função do córtex pré-frontal em estudar uma variedade de doenças, adaptação e validar esta medida comportamental em ratos é um complemento importante para a investigação sobre doenças associadas à disfunção PFC. O protocolo detalhado aqui é uma modificação do procedimento por Birrell e Brown 1, que é optimizada para a aplicação nos ratinhos, e reflecte muitas das rato-específic adaptações que foram reportados anteriormente 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>
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			<td colspan="2">Fabricated in-house, specifications can be found in protocol</td>
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			<td></td>
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			<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>
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		<tr height="21">
			<td height="21" style="height:21px;">Red Thyme</td>
			<td style="width:227px;"></td>
			<td align="right">191140</td>
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			<td height="21" style="height:21px;">Lemon</td>
			<td style="width:227px;"></td>
			<td align="right">190810</td>
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			<td height="21" style="height:21px;">Cinnamon Leaf</td>
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			<td align="right">191111</td>
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			<td height="21" style="height:21px;">Rosemary</td>
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			<td align="right">191133</td>
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			<td height="21" style="height:21px;">Citronella Java</td>
			<td style="width:227px;"></td>
			<td align="right">191112</td>
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		<tr height="21">
			<td height="21" style="height:21px;">Vanilla in jojoba oil</td>
			<td style="width:227px;"></td>
			<td align="right">191231</td>
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		<tr height="21">
			<td height="21" style="height:21px;">Anise Seed</td>
			<td style="width:227px;"></td>
			<td align="right">191102</td>
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			<td height="21" style="height:21px;">Ginger</td>
			<td style="width:227px;"></td>
			<td align="right">191121</td>
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		<tr height="21">
			<td height="21" style="height:21px;">Nutmeg</td>
			<td style="width:227px;"></td>
			<td align="right">191161</td>
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		<tr height="21">
			<td height="21" style="height:21px;"></td>
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			<td></td>
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		<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>
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		<tr height="21">
			<td height="21" style="height:21px;"></td>
			<td style="width:227px;"></td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Digging Media</td>
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			<td style="width:159px;"></td>
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		<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>
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		<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>
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		<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>
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		<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>
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		<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>
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		<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>
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		<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>
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		<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>
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		<tr height="21">
			<td height="21" style="height:21px;width:216px;"></td>
			<td style="width:227px;"></td>
			<td style="width:159px;"></td>
			<td></td>
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		<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>
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		<tr height="21">
			<td height="21" style="height:21px;width:216px;"></td>
			<td style="width:227px;"></td>
			<td style="width:159px;"></td>
			<td></td>
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		<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.

A medida dependente típico neste teste é o número de ensaios por cada fase para satisfazer o critério (ou oito escolhas correctas consecutivas). A Figura 4A mostra o número médio de ensaios para satisfazer critérios em cada fase não tratada C57BL / 6J usando a AST. Como ratinhos formar um conjunto de atenção sobre a dimensão relevante taco (odor ou meios), irá melhorar o desempenho, como indicado por uma redução em ensaios para satisfazer mudanças sucessivas no critério intradimensional,...

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

O objetivo deste protocolo é a realização de um ensaio comportamental, tais como o conjunto de atenção transferência de tarefas (AST) para avaliar a flexibilidade cognitiva prefrontal mediada pelo córtex em camundongos.

A Task Attentional Set Shifting: uma certa flexibilidade cognitiva em ratos

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 visualizações.  University of Texas Health Science Center at San Antonio.  O objetivo deste protocolo é a realização de um ensaio comportamental, tais como o conjunto de atenção transferência de tarefas (AST) para avaliar a flexibilidade cognitiva prefrontal mediada pelo córtex em camundongos. 

Vídeo: 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.

A Task Congruência Crossmodal como um meio para se obter uma medida comportamental Objetivo no Rubber Mão 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 ...

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.

A Tarefa Procedimento dupla Combinado com apresentação visual Serial rápida para testar Attentional Blink para 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.

Um operante intra / extra-dimensional Set-shift-Tarefa para ratos

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.

O emocional Stroop Task: Avaliação de Desempenho Cognitivo sob exposição a conteúdo emocional

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.

O Deese-Roediger-McDermott (DRM) Tarefa: Um Paradigma cognitivas simples para investigar Falsas Memórias no Laboratório

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.

Novas Variações para estratégia definida de mudança no Rat

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.

Apresentando Clicker Formação como um enriquecimento cognitivo para Laboratório Mice

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.

O "Motor" em Motor implícita sequência de aprendizagem: uma reação Serial depuração pé tempo tarefa

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.

Olho de monitoramento durante a compreensão de linguagem visualmente situado: Flexibilidade e limitações no descobrindo contexto Visual Effects

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.

Usando Rapid Serial Visual Presentation para medir o conjunto específico captura, uma consequência da distração enquanto multitarefa

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