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1.
Can J Exp Psychol ; 73(4): 254-264, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31393154

RESUMO

The production effect is defined as better memory for items that were read aloud compared with items that were read silently. Quinlan and Taylor (2013) expanded the findings of the production effect by demonstrating that singing items produces even better recognition performance than reading aloud, and argued that this was due to enhanced relative distinctiveness. The current study tested three alternative accounts. In Experiment 1, we explored whether singing results in a larger production effect because it is deemed more bizarre than reading aloud. To address this, we tested a sample for whom singing does not seem bizarre: experienced singers. They also showed better recognition of items that were sung compared with those that were read aloud. In Experiment 2, we determined that singing appears to take longer than either reading aloud or reading silently; however, the possible effect of production time was further explored in Experiment 3. We did this by instructing participants to sing quickly, read aloud slowly, or read silently. Altering relative production times resulted in no discernible changes in subsequent recognition performance. Finally, in Experiment 4, we explored whether singing might strengthen the memory trace relative to reading aloud. We tested this by manipulating the production instruction between subjects. This eliminated the recognition advantage for both reading items aloud as well as for singing them aloud. Having ruled out these alternatives, we argue that singing improves subsequent recognition because it offers more distinctive elements than either reading aloud or reading silently. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

2.
J Med Chem ; 62(7): 3228-3250, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30893553

RESUMO

Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fcε receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacological inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clinical studies.

3.
J Med Chem ; 62(5): 2265-2285, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30785748

RESUMO

Recently, our research group reported the identification of BMS-986104 (2) as a differentiated S1P1 receptor modulator. In comparison to fingolimod (1), a full agonist of S1P1 currently marketed for the treatment of relapse remitting multiple sclerosis (RRMS), 2 offers several potential advantages having demonstrated improved safety multiples in preclinical evaluations against undesired pulmonary and cardiovascular effects. In clinical trials, 2 was found to exhibit a pharmacokinetic half-life ( T1/2) longer than that of 1, as well as a reduced formation of the phosphate metabolite that is required for activity against S1P1. Herein, we describe our efforts to discover highly potent, partial agonists of S1P1 with a shorter T1/2 and increased in vivo phosphate metabolite formation. These efforts culminated in the discovery of BMS-986166 (14a), which was advanced to human clinical evaluation. The pharmacokinetic/pharmacodynamic (PK/PD) relationship as well as pulmonary and cardiovascular safety assessments are discussed. Furthermore, efficacy of 14a in multiple preclinical models of autoimmune diseases are presented.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30194621

RESUMO

In an item-method directed forgetting task, attentional resources are withdrawn from forget item processing (e.g., Taylor & Fawcett in Attention, Perception, & Psychophysics, 73, 1790-1814, 2011). Taylor and Hamm (Attention, Perception, & Psychophysics, 78, 168-186, 2016) demonstrated that there is no corresponding increase in the proclivity for exogenous attention to be captured following a forget instruction. This means either that the attentional resources withdrawn from the forget item are reallocated immediately (and therefore not especially vulnerable to capture) or that it is not exogenous attention that is withdrawn. Given that endogenous attention is distinct from exogenous attention, we therefore extended the Taylor and Hamm study by using endogenous orienting rather than exogenous orienting. Words appeared individually in a peripheral location (Exp. 1) or in a central location (Exp. 2), followed by an instruction to either remember or forget. After a short (50-ms) or long (250-ms) interstimulus interval (ISI), a central cue (80% accurate) directed participants to allocate their attention to the left or right. This was followed by a discrimination target that appeared at a 1,000-ms cue-target stimulus onset asynchrony. A subsequent yes-no recognition test assessed memory for all study items. In both experiments, we observed better recognition of remember words than forget words-a directed forgetting effect. We also found a cueing effect, revealed as faster reaction times to discriminate cued targets than to discriminate uncued targets. There was not, however, an effect of memory instruction (and/or instruction-cue ISI) on the magnitude of this cueing effect. Thus, neither exogenous attention nor endogenous attention remains in an unengaged state following an instruction to forget.

5.
Acta Psychol (Amst) ; 188: 39-54, 2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29857288

RESUMO

Using an item-method directed forgetting task, we presented homographic homophonic nouns embedded in sentences. At study, each sentence was followed by an instruction to remember or forget the embedded word. On a subsequent yes-no recognition test, each word was again embedded within a sentence. In Experiments 1, 2, and 4 we varied the embedding sentence at test so that it was identical to that at study, changed but retained the meaning of the studied word, or changed to alter the meaning of the studied word. Repeated context - whether the sentence and/or the word meaning - proved to be as useful a retrieval cue for TBF items as for TBR items. In Experiment 3, we demonstrated that physical repetition was insufficient to produce context effects for either TBR or TBF items. And, in Experiment 4, we determined that participants were equally accurate in reporting context repetition/change following the correct recognition of TBR and TBF items. When considered in light of the existing literature, our results suggest that when context can be dissociated from the study item, it is encoded in "one shot" and not vulnerable to subsequent efforts to limit unwanted encoding.

6.
Atten Percept Psychophys ; 80(6): 1489-1503, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29691764

RESUMO

This study used rapid serial visual presentation (RSVP) to determine whether, in an item-method directed forgetting task, study word processing ends earlier for forget words than for remember words. The critical manipulation required participants to monitor an RSVP stream of black nonsense strings in which a single blue word was embedded. The next item to follow the word was a string of red fs that instructed the participant to forget the word or green rs that instructed the participant to remember the word. After the memory instruction, a probe string of black xs or os appeared at postinstruction positions 1-8. Accuracy in reporting the identity of the probe string revealed an attenuated attentional blink following instructions to forget. A yes-no recognition task that followed the study trials confirmed a directed forgetting effect, with better recognition of remember words than forget words. Considered in the context of control conditions that required participants to commit either all or none of the study words to memory, the pattern of probe identification accuracy following the directed forgetting task argues that an intention to forget releases limited-capacity attentional resources sooner than an instruction to remember-despite participants needing to maintain an ongoing rehearsal set in both cases.

7.
Acta Psychol (Amst) ; 183: 116-123, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29275948

RESUMO

In an item-method directed forgetting paradigm, words are presented one at a time, each followed by an instruction to Remember or Forget; a directed forgetting effect is measured as better subsequent memory for Remember words than Forget words. The dominant view is that the directed forgetting effect arises during encoding due to selective rehearsal of Remember over Forget items. In three experiments we attempted to falsify a strong view that directed forgetting effects in recognition are due only to encoding mechanisms when an item method is used. Across 3 experiments we tested for retrieval-based processes by colour-coding the recognition test items. Black colour provided no information; green colour cued a potential Remember item; and, red colour cued a potential Forget item. Recognition cues were mixed within-blocks in Experiment 1 and between-blocks in Experiments 2 and 3; Experiment 3 added explicit feedback on the accuracy of the recognition decision. Although overall recognition improved with cuing when explicit test performance feedback was added in Experiment 3, in no case was the magnitude of the directed forgetting effect influenced by recognition cueing. Our results argue against a role for retrieval-based strategies that limit recognition of Forget items at test and posit a role for encoding intentions only.


Assuntos
Aprendizagem/fisiologia , Memória/fisiologia , Rememoração Mental/fisiologia , Recognição (Psicologia)/fisiologia , Sinais (Psicologia) , Feminino , Humanos , Masculino , Adulto Jovem
8.
Mem Cognit ; 46(1): 132-147, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29214552

RESUMO

Using an item-method directed forgetting task, we presented negative, neutral, and positive photographic pictures, one at a time, each followed by an instruction to remember or forget. We determined that the directed forgetting effect, defined as better subsequent recognition of to-be-remembered (TBR) items than to-be-forgotten (TBF) items, was equivalent across negative, neutral, and positive pictures. To disentangle the underlying costs (i.e., decrease in memory for TBF items) and benefits (i.e., increase in memory for TBR items), we compared recognition memory performance in the directed forgetting task to that of a novel within-subjects remember-all control condition (Experiment 1) and to a between-subjects remember-all control group (Experiment 2). We observed costs without benefits across all three emotions-negative, neutral, and positive-in both experiments. These results demonstrate that equivalent directed forgetting effects for emotional stimuli are not attributable to different underlying component processes. Instead, our results suggest that selection for encoding is accomplished in similar ways, regardless of emotional content.

9.
PLoS One ; 12(7): e0181782, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28742141

RESUMO

Bruton's tyrosine kinase (BTK) regulates critical signal transduction pathways involved in the pathobiology of rheumatoid arthritis (RA) and other autoimmune disorders. BMS-986142 is a potent and highly selective reversible small molecule inhibitor of BTK currently being investigated in clinical trials for the treatment of both RA and primary Sjögren's syndrome. In the present report, we detail the in vitro and in vivo pharmacology of BMS-986142 and show this agent provides potent and selective inhibition of BTK (IC50 = 0.5 nM), blocks antigen receptor-dependent signaling and functional endpoints (cytokine production, co-stimulatory molecule expression, and proliferation) in human B cells (IC50 ≤ 5 nM), inhibits Fcγ receptor-dependent cytokine production from peripheral blood mononuclear cells, and blocks RANK-L-induced osteoclastogenesis. Through the benefits of impacting these important drivers of autoimmunity, BMS-986142 demonstrated robust efficacy in murine models of rheumatoid arthritis (RA), including collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA). In both models, robust efficacy was observed without continuous, complete inhibition of BTK. When a suboptimal dose of BMS-986142 was combined with other agents representing the current standard of care for RA (e.g., methotrexate, the TNFα antagonist etanercept, or the murine form of CTLA4-Ig) in the CIA model, improved efficacy compared to either agent alone was observed. The results suggest BMS-986142 represents a potential therapeutic for clinical investigation in RA, as monotherapy or co-administered with agents with complementary mechanisms of action.


Assuntos
Artrite Experimental/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Tirosina Quinase da Agamaglobulinemia , Animais , Formação de Anticorpos/efeitos dos fármacos , Artrite Experimental/imunologia , Artrite Experimental/patologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/patologia , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Camundongos Endogâmicos BALB C , Osteoclastos/efeitos dos fármacos , Osteoclastos/imunologia , Osteoclastos/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/imunologia , Ligante RANK/imunologia
10.
Medchemcomm ; 8(4): 725-729, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30108791

RESUMO

Recently, our research group reported the identification of prodrug amino-alcohol 2 as a potent and efficacious S1P1 receptor modulator. This molecule is differentiated preclinically over the marketed drug fingolimod (Gilenya 1), whose active phosphate metabolite is an S1P1 full agonist, in terms of pulmonary and cardiovascular safety. S1P1 partial agonist 2, however, has a long half-life in rodents and was projected to have a long half-life in humans. The purpose of this communication is to disclose highly potent partial agonists of S1P1 with shorter half-lives relative to the clinical compound 2. PK/PD relationships as well as their preclinical pulmonary and cardiovascular safety assessment are discussed.

11.
J Med Chem ; 59(24): 11138-11147, 2016 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-28002964

RESUMO

We describe a highly efficient route for the synthesis of 4a (BMS-986104). A key step in the synthesis is the asymmetric hydroboration of trisubstituted alkene 6. Particularly given the known difficulties involved in this type of transformation (6 → 7), the current methodology provides an efficient approach to prepare this class of compounds. In addition, we disclose the efficacy of 4a in a mouse EAE model, which is comparable to 4c (FTY720). Mechanistically, 4a exhibited excellent remyelinating effects on lysophosphatidylcholine (LPC) induced demyelination in a three-dimensional brain cell culture assay.


Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Naftalenos/farmacologia , Receptores de Lisoesfingolipídeo/agonistas , Animais , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Células HEK293 , Humanos , Linfócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Estrutura Molecular , Naftalenos/síntese química , Naftalenos/química , Relação Estrutura-Atividade
12.
J Med Chem ; 59(21): 9837-9854, 2016 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-27726358

RESUMO

Fingolimod (1) is the first approved oral therapy for the treatment of relapsing remitting multiple sclerosis. While the phosphorylated metabolite of fingolimod was found to be a nonselective S1P receptor agonist, agonism specifically of S1P1 is responsible for the peripheral blood lymphopenia believed to be key to its efficacy. Identification of modulators that maintain activity on S1P1 while sparing activity on other S1P receptors could offer equivalent efficacy with reduced liabilities. We disclose in this paper a ligand-based drug design approach that led to the discovery of a series of potent tricyclic agonists of S1P1 with selectivity over S1P3 and were efficacious in a pharmacodynamic model of suppression of circulating lymphocytes. Compound 10 had the desired pharmacokinetic (PK) and pharmacodynamic (PD) profile and demonstrated maximal efficacy when administered orally in a rat adjuvant arthritis model.


Assuntos
Desenho de Drogas , Cloridrato de Fingolimode/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Receptores de Lisoesfingolipídeo/agonistas , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Cães , Relação Dose-Resposta a Droga , Cloridrato de Fingolimode/administração & dosagem , Cloridrato de Fingolimode/química , Adjuvante de Freund/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/química , Ligantes , Linfócitos/efeitos dos fármacos , Macaca fascicularis , Masculino , Camundongos , Estrutura Molecular , Mycobacterium/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew , Relação Estrutura-Atividade , Distribuição Tecidual
13.
J Med Chem ; 59(19): 9173-9200, 2016 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-27583770

RESUMO

Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, is a member of the Tec family of kinases. BTK plays an essential role in B cell receptor (BCR)-mediated signaling as well as Fcγ receptor signaling in monocytes and Fcε receptor signaling in mast cells and basophils, all of which have been implicated in the pathophysiology of autoimmune disease. As a result, inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as lupus and rheumatoid arthritis. This article details the structure-activity relationships (SAR) leading to a novel series of highly potent and selective carbazole and tetrahydrocarbazole based, reversible inhibitors of BTK. Of particular interest is that two atropisomeric centers were rotationally locked to provide a single, stable atropisomer, resulting in enhanced potency and selectivity as well as a reduction in safety liabilities. With significantly enhanced potency and selectivity, excellent in vivo properties and efficacy, and a very desirable tolerability and safety profile, 14f (BMS-986142) was advanced into clinical studies.


Assuntos
Carbazóis/química , Carbazóis/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Tirosina Quinase da Agamaglobulinemia , Animais , Carbazóis/farmacocinética , Cristalografia por Raios X , Feminino , Humanos , Isomerismo , Macaca fascicularis , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Inibidores de Proteínas Quinases/farmacocinética , Proteínas Tirosina Quinases/metabolismo , Quinazolinas/química , Quinazolinas/farmacocinética , Quinazolinas/farmacologia , Relação Estrutura-Atividade
14.
Can J Exp Psychol ; 70(2): 139-46, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27244355

RESUMO

Items that are produced (e.g., read aloud) during encoding typically are better remembered than items that are not produced (e.g., read silently). This "production effect" has been explained by distinctiveness: Produced items have more distinct features than nonproduced items, leading to enhanced retrieval. The goal of the current study was to use electroencephalography (EEG) to examine the neural basis of the production effect. During study, participants were presented with words that they were required to read silently, read aloud, or sing while EEG data were recorded. Subsequent memory performance was tested using a yes/no recognition test. Analysis focused on the event-related brain potentials (ERPs) evoked by the encoding instruction cue for each instruction condition. Our data revealed enhanced memory performance for produced items and a greater P300 ERP amplitude for instructions to sing or read aloud compared with instructions to read silently. Our results demonstrate that the amplitude of the P300 is modulated by at least 1 aspect of production, vocalization (singing/reading aloud relative to reading silently), and are consistent with the distinctiveness account of the production effect. The ERP methodology is a viable tool for investigating the production effect. (PsycINFO Database Record


Assuntos
Potencial Evocado P300/fisiologia , Leitura , Recognição (Psicologia)/fisiologia , Canto/fisiologia , Fala/fisiologia , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Adulto Jovem
15.
ACS Med Chem Lett ; 7(3): 283-8, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26985316

RESUMO

Clinical validation of S1P receptor modulation therapy was achieved with the approval of fingolimod (Gilenya, 1) as the first oral therapy for relapsing remitting multiple sclerosis. However, 1 causes a dose-dependent reduction in the heart rate (bradycardia), which occurs within hours after first dose. We disclose the identification of clinical compound BMS-986104 (3d), a novel S1P1 receptor modulator, which demonstrates ligand-biased signaling and differentiates from 1 in terms of cardiovascular and pulmonary safety based on preclinical pharmacology while showing equivalent efficacy in a T-cell transfer colitis model.

16.
Atten Percept Psychophys ; 78(1): 168-86, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26404529

RESUMO

We measured attentional orienting in an item-method-directed forgetting task. Words appeared singly, followed by an instruction to remember or forget. In Experiment 1, study words appeared at center; in Experiments 2 and 3, they appeared to the left and right. In all three experiments, there was a delay of 50 ms or 250 ms, after which a cue appeared to the left or right of fixation. This was followed at a fixed 100-ms stimulus onset asynchrony by a target in the cued or uncued location. Attentional capture was measured by evaluating the speed to localize (Experiments 1 and 2) or discriminate (Experiment 3) targets in cued versus uncued locations. A subsequent yes-no recognition test confirmed a directed forgetting effect. Even though attention is purported to withdraw more readily after forget instructions than after remember instructions, we obtained no evidence for the corollary: Attention is not more readily captured by events that follow forget instructions. A forget instruction must therefore impact attention only insofar as withdrawal is needed to instantiate the intention to forget, without instigating a longer lasting distractibility.


Assuntos
Atenção/fisiologia , Rememoração Mental/fisiologia , Adulto , Sinais (Psicologia) , Humanos , Intenção , Orientação , Fatores de Tempo
17.
J Exp Psychol Gen ; 145(1): 56-81, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26709589

RESUMO

We investigated whether intentional forgetting impacts only the likelihood of later retrieval from long-term memory or whether it also impacts the fidelity of those representations that are successfully retrieved. We accomplished this by combining an item-method directed forgetting task with a testing procedure and modeling approach inspired by the delayed-estimation paradigm used in the study of visual short-term memory (STM). Abstract or concrete colored images were each followed by a remember (R) or forget (F) instruction and sometimes by a visual probe requiring a speeded detection response (E1-E3). Memory was tested using an old-new (E1-E2) or remember-know-no (E3) recognition task followed by a continuous color judgment task (E2-E3); a final experiment included only the color judgment task (E4). Replicating the existing literature, more "old" or "remember" responses were made to R than F items and RTs to postinstruction visual probes were longer following F than R instructions. Color judgments were more accurate for successfully recognized or recollected R than F items (E2-E3); a mixture model confirmed a decrease to both the probability of retrieving the F items as well as the fidelity of the representation of those F items that were retrieved (E4). We conclude that intentional forgetting is an effortful process that not only reduces the likelihood of successfully encoding an item for later retrieval, but also produces an impoverished memory trace even when those items are retrieved; these findings draw a parallel between the control of memory representations within working and long-term memory.


Assuntos
Atenção , Intenção , Reconhecimento Visual de Modelos , Probabilidade , Repressão Psicológica , Retenção (Psicologia) , Feminino , Humanos , Julgamento , Funções Verossimilhança , Masculino , Rememoração Mental , Tempo de Reação , Recognição (Psicologia) , Adulto Jovem
18.
J Med Chem ; 58(19): 7775-84, 2015 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-26359680

RESUMO

In search for prodrugs to address the issue of pH-dependent solubility and exposure associated with 1 (BMS-582949), a previously disclosed phase II clinical p38α MAP kinase inhibitor, a structurally novel clinical prodrug, 2 (BMS-751324), featuring a carbamoylmethylene linked promoiety containing hydroxyphenyl acetic acid (HPA) derived ester and phosphate functionalities, was identified. Prodrug 2 was not only stable but also water-soluble under both acidic and neutral conditions. It was effectively bioconverted into parent drug 1 in vivo by alkaline phosphatase and esterase in a stepwise manner, providing higher exposure of 1 compared to its direct administration, especially within higher dose ranges. In a rat LPS-induced TNFα pharmacodynamic model and a rat adjuvant arthritis model, 2 demonstrated similar efficacy to 1. Most importantly, it was shown in clinical studies that prodrug 2 was indeed effective in addressing the pH-dependent absorption issue associated with 1.


Assuntos
Organofosfatos/farmacologia , Fenilacetatos/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Administração Oral , Animais , Artrite Experimental/tratamento farmacológico , Disponibilidade Biológica , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Macaca fascicularis , Masculino , Proteína Quinase 14 Ativada por Mitógeno/antagonistas & inibidores , Estrutura Molecular , Organofosfatos/química , Fenilacetatos/química , Pró-Fármacos/farmacocinética , Inibidores de Proteínas Quinases/química , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Solubilidade , Relação Estrutura-Atividade
19.
Atten Percept Psychophys ; 77(3): 804-18, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25592783

RESUMO

In the item-method directed forgetting paradigm, the magnitude of inhibition of return (IOR) is larger after an instruction to forget (F) than after an instruction to remember (R). In the present experiments, we further investigated this increased magnitude of IOR after F than after R memory instructions, to determine whether this F > R IOR pattern occurs only for the motoric form of IOR, as predicted, or also for the visual form. In three experiments, words were presented in one of two peripheral locations, followed by either an F or an R memory instruction. Then, a target appeared either at the same location as the previous word or at the other location. In Experiment 1, participants maintained fixation throughout the trial until the target appeared, at which point they made a saccade to the target. In Experiment 2, they maintained fixation throughout the entire trial and made a manual localization response to the target. The F > R IOR difference in reaction times occurred for both the saccadic and manual responses, suggesting that memory instructions modify both motoric and visual forms of IOR. In Experiment 3, participants made a perceptual discrimination response to report the identity of a target while the eyes remained fixed. The F > R IOR difference also occurred for these manual discrimination responses, increasing our confidence that memory instructions modify the visual form of IOR. We relate our findings to postulated differences in attentional withdrawal following F and R instructions and consider the implications of the findings for successful forgetting.


Assuntos
Atenção/fisiologia , Inibição (Psicologia) , Memória/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Sinais (Psicologia) , Feminino , Voluntários Saudáveis , Humanos , Masculino , Rememoração Mental , Tempo de Reação/fisiologia , Recognição (Psicologia)/fisiologia , Movimentos Sacádicos , Adulto Jovem
20.
Can J Exp Psychol ; 68(3): 212-21, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25383479

RESUMO

The current study used the item-method directed forgetting paradigm to determine whether there are limits on the ability to intentionally forget angry faces. During the study phase, faces were presented, 1 at a time, each followed by an instruction to remember or forget. Following the presentation of all faces, participants performed a yes-no recognition test. In 2 experiments that varied only the presentation duration of the face (500 ms vs. 1,000 ms), we observed an overall directed forgetting effect, with greater recognition of faces studied with remember rather than forget instructions; the magnitude of this effect did not vary with emotional expression. We interpret these results in light of the proposal that priority processing of angry faces benefits the speed of forming an enduring long-term memory trace rather than increasing the strength of that trace.


Assuntos
Emoções/fisiologia , Expressão Facial , Intenção , Memória/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Feminino , Humanos , Masculino , Estimulação Luminosa , Estudantes , Universidades
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