Inhibitory control in memory: evidence for negative priming in free recall

Cognitive control mechanisms—such as inhibition—decrease the likelihood that goal-directed activity is ceded to irrelevant events. Here, we use the action of auditory distraction to show how retrieval from episodic long-term memory is affected by competitor inhibition. Typically, a sequence of to-be-ignored spoken distracters drawn from the same semantic category as a list of visually-presented to-be-recalled items impairs free recall performance. In line with competitor inhibition theory (Anderson, 2003), free recall was worse for items on a probe trial if they were a repeat of distracter items presented during the previous, prime, trial (Experiment 1). This effect was only produced when the distracters were dominant members of the same category as the to-be-recalled items on the prime. For prime trials in which distracters were low-dominant members of the to-be-remembered item category or were unrelated to that category—and hence not strong competitors for retrieval—positive priming was found (Experiments 2 & 3). These results are discussed in terms of inhibitory approaches to negative priming and memory retrieval.

Risk-taking and inhibitory control in behaviourally inhibited and disinhibited preschool children

The temperament style Behavioural Inhibition (BI) has been implicated as a risk factor for the development of internalising disorders such as anxiety. Of interest is what factors influence the developmental trajectories of both inhibited and disinhibited children and the development of psychopathology. One such factor is risk-taking behaviour. Using the computer based Balloon Analogue Risk Task, we assessed risk taking behaviour in behaviourally inhibited (n = 27) and behaviourally disinhibited (n = 43) children. This is the first study to examine the relationship between BI, executive functioning and risk-taking. The results indicated Behavioural Inhibition was not related to risk-taking but that inhibitory control predicted reward focused results. These findings illustrate how inhibitory control affects risk-taking and risk avoidance in both inhibited and disinhibited children.

Negative priming in free recall reconsidered

Recent investigations of the phenomenon of forgetting have been driven mostly by the development of a novel theoretical framework which places great emphasis on inhibitory control (Anderson, 2003; Anderson & Spellman, 1995; Bjork, 1989). Whereas traditional, interference-based theories consider forgetting to be a by-product of storing new information, the inhibitory framework postulates a specialized mechanism, or a group of mechanisms, that serves the function of ‘deactivating’ information which is currently irrelevant. This process of inhibiting currently irrelevant information is thought to have lasting consequences, affecting memory for the irrelevant information on subsequent tests. The active and functional perspective on forgetting embedded in the inhibitory framework opens new fields for examining the role of forgetting in cognitive functioning. Differences in the ability to inhibit irrelevant information have been postulated to play important roles in a range of clinical conditions (e.g., Soriano, Jiménez, Román, & Bajo, 2009; Storm & White, 2010) and the trajectory of cognitive development (e.g., Aslan & Bäuml, 2010) as well as contributing to individual differences in many other cognitive and social domains (Redick, Heitz, & Engle, 2007).

Platelet 12-lipoxygenase activation via glycoprotein VI: involvement of multiple signaling pathways in agonist control of H(P)ETE synthesis

Lipoxygenases (LOX) contribute to vascular disease and inflammation through generation of bioactive lipids, including 12-hydro(pero xyeicosatetraenoic acid (12-H(P)ETE). The physiological mechanisms that acutely control LOX product generation in mammalian cells are uncharacterized. Human platelets that contain a 12-LOX isoform (p12-LOX) were used to define pathways that activate H(P)ETE synthesis in the vasculature. Collagen and collagen-related peptide (CRP) (1 to 10 g/mL) acutely induced platelet 12-H(P)ETE synthesis. This implicated the collagen receptor glycoprotein VI (GPVI), which signals via the immunoreceptor-based activatory motif (ITAM)- containing FcR chain. Conversely, thrombin only activated at high concentrations ( 0.2 U/mL), whereas U46619 and ADP alone were ineffective. Collagen or CRP-stimulated 12-H(P)ETE generation was inhibited by staurosporine, PP2, wortmannin, BAPTA/AM, EGTA, and L-655238, implicating src-tyrosine kinases, PI3-kinase, Ca2 mobilization, and p12-LOX translocation. In contrast, protein kinase C (PKC) inhibition potentiated 12-H(P)ETE generation. Finally, activation of the immunoreceptor tyrosine-based inhibitory motif (ITIM)– containing platelet endothelial cell adhesion molecule (PECAM-1) inhibited p12-LOX product generation. This study characterizes a receptor-dependent pathway for 12-H(P)ETE synthesis via the collagen receptor GPVI, which is negatively regulated by PECAM-1 and PKC, and demonstrates a novel link between immune receptor signaling and lipid mediator generation in the vasculature. (Circ Res. 2004;94:1598-1605.)

Identification of stimulatory and inhibitory inputs to the hypothalamic-pituitary-adrenal axis during hypoglycaemia or transport in ewes

This study used the novel approach of statistical modelling to investigate the control of hypothalamic-pituitary-adrenal (HPA) axis and quantify temporal relationships between hormones. Two experimental paradigms were chosen, insulin-induced hypoglycaemia and 2 h transport, to assess differences in control between noncognitive and cognitive stimuli. Vasopressin and corticotropin-releasing hormone (CRH) were measured in hypophysial portal plasma, and adrenocorticotropin hormone (ACTH) and cortisol in jugular plasma of conscious sheep, and deconvolution analysis was used to calculate secretory rates, before modelling. During hypoglycaemia, the relationship between plasma glucose and vasopressin or CRH was best described by log(10) transforming variables (i.e. a positive power-curve relationship). A negative-feedback relationship with log(10) cortisol concentration 2 h previously was detected. Analysis of the 'transport' stimulus suggested that the strength of the perceived stimulus decreased over time after accounting for cortisol facilitation and negative-feedback. The time course of vasopressin and CRH responses to each stimulus were different However, at the pituitary level, the data suggested that log(10) ACTH secretion rate was related to log(10) vasopressin and CRH concentrations with very similar regression coefficients and an identical ratio of actions (2.3 : 1) for both stimuli. Similar magnitude negative-feedback effects of log(10) cortisol at -110 min (hypoglycaemia) or -40 min (transport) were detected, and both models contained a stimulatory relationship with cortisol at 0 min (facilitation). At adrenal gland level, cortisol secretory rates were related to simultaneously measured untransformed ACTH concentration but the regression coefficient for the hypoglycaemia model was 2.5-fold greater than for transport. No individual sustained maximum cortisol secretion for longer than 20 min during hypoglycaemia and 40 min during transport. These unique models demonstrate that corticosteroid negative-feedback is a significant control mechanism at both the pituitary and hypothalamus. The amplitude of HPA response may be related to stimulus intensity and corticosteroid negative-feedback, while duration depended on feedback alone.

Inhibitory effects of olive oil phenolics on invasion in human colon adenocarcinoma cells in vitro

Studies in human, animal and cellular systems suggest that phenols from virgin olive oil are capable of inhibiting several stages in carcinogenesis, including metastasis. The invasion cascade comprises cell attachment to extracellular matrix components or basement membrane, degradation of basement membrane by proteolytic enzymes and migration of cells through the modified matrix. In the present study, we investigated the effect of phenolics extracted from virgin olive oil (OVP) and its main constituents: hydroxytyrosol (3,4-dihydroxyphenylethanol), tyrosol (p-hydroxyphenylethanol), pinoresinol and caffeic acid. The effects of these phenolics were tested on the invasion of HT115 human colon carcinoma cells in a Matrigel invasion assay. OVP and its compounds showed different dose-related anti-invasive effects. At 25 mu g/ml OVP and equivalent doses of individual compounds, significant anti-invasive effects were seen in the range of 45-55% of control. Importantly, OVP, but not the isolated phenolics, significantly reduced total cell number in the Matrigel invasion assay. There were no significant effects shown on cell viability, indicating the reduction of cell number in the Matrigel invasion assay was not due to cytotoxicity. There were also no significant effects on cell attachment to plastic substrate, indicating the importance of extracellular matrix in modulating the anti-invasive effects of OVP. In conclusion, the results from this study indicate that phenols from virgin olive oil have the ability to inhibit invasion of colon cancer cells and the effects may be mediated at different levels of the invasion cascade. (c) 2007 Wiley-Liss, Inc.

The neurochemically diverse intermedius nucleus of the medulla as a source of excitatory and inhibitory synaptic input to the nucleus tractus solitarii

Sensory afferent signals from neck muscles have been postulated to influence central cardiorespiratory control as components of postural reflexes, but neuronal pathways for this action have not been identified. The intermedius nucleus of the medulla (InM) is a target of neck muscle spindle afferents and is ideally located to influence such reflexes but is poorly investigated. To aid identification of the nucleus, we initially produced three-dimensional reconstructions of the InM in both mouse and rat. Neurochemical analysis including transgenic reporter mice expressing green fluorescent protein in GABA-synthesizing neurons, immunohistochemistry, and in situ hybridization revealed that the InM is neurochemically diverse, containing GABAegric and glutamatergic neurons with some degree of colocalization with parvalbumin, neuronal nitric oxide synthase, and calretinin. Projections from the InM to the nucleus tractus solitarius (NTS) were studied electrophysiologically in rat brainstem slices. Electrical stimulation of the NTS resulted in antidromically activated action potentials within InM neurons. In addition, electrical stimulation of the InM resulted in EPSPs that were mediated by excitatory amino acids and IPSPs mediated solely by GABA(A) receptors or by GABA(A) and glycine receptors. Chemical stimulation of the InM resulted in (1) a depolarization of NTS neurons that were blocked by NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonoamide) or kynurenic acid and (2) a hyperpolarization of NTS neurons that were blocked by bicuculline. Thus, the InM contains neurochemically diverse neurons and sends both excitatory and inhibitory projections to the NTS. These data provide a novel pathway that may underlie possible reflex changes in autonomic variables after neck muscle spindle afferent activation.

Platelet signaling: a complex interplay between inhibitory and activatory networks

The role of platelets in hemostasis and thrombosis is dependent on a complex balance of activatory and inhibitory signaling pathways. Inhibitory signals released from the healthy vasculature suppress platelet activation in the absence of platelet receptor agonists. Activatory signals present at a site of injury initiate platelet activation and thrombus formation; subsequently, endogenous negative signaling regulators dampen activatory signals to control thrombus growth. Understanding the complex interplay between activatory and inhibitory signaling networks is an emerging challenge in the study of platelet biology and necessitates a systematic approach to utilize experimental data effectively. In this review, we will explore the key points of platelet regulation and signaling that maintain platelets in a resting state, mediate activation to elicit thrombus formation or provide negative feedback. Platelet signaling will be described in terms of key signaling molecules that are common to the pathways activated by platelet agonists and can be described as regulatory nodes for both positive and negative regulators. This article is protected by copyright. All rights reserved.

Effects of dense code-switching on executive control

Bilingualism is reported to re-structure executive control networks, but it remains unknown which aspects of the bilingual experience cause this modulation. This study explores the impact of three code-switching types on executive functions: (1) alternation of languages, (2) insertion of lexicon of one language into grammar of another, (3) dense code-switching with co-activation of lexicon and grammar. Current models hypothesise that they challenge different aspects of the executive system because they vary in the extent and scope of language separation. Two groups of German-English bilinguals differing in dense code-switching frequency participated in a flanker task under conditions varying in degree of trial-mixing and resulting demands to conflict-monitoring. Bilinguals engaging in more dense code-switching showed inhibitory advantages in the condition requiring most conflict-monitoring. Moreover, dense code-switching frequency correlated positively with monitoring skills. This suggests that the management of co-activated languages during dense code-switching engages conflict-monitoring and that the consolidation processes taking place within co-activated linguistic systems involve local inhibition. Code-switching types requiring greater degrees of language separation may involve more global forms of inhibition. This study shows that dense code-switching is a key experience shaping bilinguals’ executive functioning and highlights the importance of controlling for participants’ code-switching habits in bilingualism research.