Controlling natural killer cell responses: integration of signals for activation and inhibition.

Understanding how signals are integrated to control natural killer (NK) cell responsiveness in the absence of antigen-specific receptors has been a challenge, but recent work has revealed some underlying principles that govern NK cell responses. NK cells use an array of innate receptors to sense their environment and respond to alterations caused by infections, cellular stress, and transformation. No single activation receptor dominates; instead, synergistic signals from combinations of receptors are integrated to activate natural cytotoxicity and cytokine production. Inhibitory receptors for major histocompatibility complex class I (MHC-I) have a critical role in controlling NK cell responses and, paradoxically, in maintaining NK cells in a state of responsiveness to subsequent activation events, a process referred to as licensing. MHC-I-specific inhibitory receptors both block activation signals and trigger signals to phosphorylate and inactivate the small adaptor Crk. These different facets of inhibitory signaling are incorporated into a revocable license model for the reversible tuning of NK cell responsiveness.

Autoantibodies inhibit Plasmodium falciparum growth and are associated with protection from clinical malaria.

Many infections, including malaria, are associated with an increase in autoantibodies (AAbs). Prior studies have reported an association between genetic markers of susceptibility to autoimmune disease and resistance to malaria, but the underlying mechanisms are unclear. Here, we performed a longitudinal study of children and adults (n = 602) in Mali and found that high levels of plasma AAbs before the malaria season independently predicted a reduced risk of clinical malaria in children during the ensuing malaria season. Baseline AAb seroprevalence increased with age and asymptomatic Plasmodium falciparum infection. We found that AAbs purified from the plasma of protected individuals inhibit the growth of blood-stage parasites and bind P. falciparum proteins that mediate parasite invasion. Protected individuals had higher plasma immunoglobulin G (IgG) reactivity against 33 of the 123 antigens assessed in an autoantigen microarray. This study provides evidence in support of the hypothesis that a propensity toward autoimmunity offers a survival advantage against malaria.

Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria.

BACKGROUND: Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from P. falciparum infection in a region where this organism is endemic is unclear. METHODS: We conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season. In part A of the trial, safety was assessed at three dose levels in adults, followed by assessment at two dose levels in children. In part B of the trial, children were randomly assigned, in a 1:1:1 ratio, to receive 150 mg of L9LS, 300 mg of L9LS, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection, as detected on blood smear performed at least every 2 weeks for 24 weeks. A secondary efficacy end point was the first episode of clinical malaria, as assessed in a time-to-event analysis. RESULTS: No safety concerns were identified in the dose-escalation part of the trial (part A). In part B, 225 children underwent randomization, with 75 children assigned to each group. No safety concerns were identified in part B. P. falciparum infection occurred in 36 participants (48%) in the 150-mg group, in 30 (40%) in the 300-mg group, and in 61 (81%) in the placebo group. The efficacy of L9LS against P. falciparum infection, as compared with placebo, was 66% (adjusted confidence interval [95% CI], 45 to 79) with the 150-mg dose and 70% (adjusted 95% CI, 50 to 82) with the 300-mg dose (P<0.001 for both comparisons). Efficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons). CONCLUSIONS: Subcutaneous administration of L9LS to children was protective against P. falciparum infection and clinical malaria over a period of 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05304611.).

Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali.

BACKGROUND: CIS43LS is a monoclonal antibody that was shown to protect against controlled Plasmodium falciparum infection in a phase 1 clinical trial. Whether a monoclonal antibody can prevent P. falciparum infection in a region in which the infection is endemic is unknown. METHODS: We conducted a phase 2 trial to assess the safety and efficacy of a single intravenous infusion of CIS43LS against P. falciparum infection in healthy adults in Mali over a 6-month malaria season. In Part A, safety was assessed at three escalating dose levels. In Part B, participants were randomly assigned (in a 1:1:1 ratio) to receive 10 mg of CIS43LS per kilogram of body weight, 40 mg of CIS43LS per kilogram, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection detected on blood-smear examination, which was performed at least every 2 weeks for 24 weeks. At enrollment, all the participants received artemether-lumefantrine to clear possible P. falciparum infection. RESULTS: In Part B, 330 adults underwent randomization; 110 were assigned to each trial group. The risk of moderate headache was 3.3 times as high with 40 mg of CIS43LS per kilogram as with placebo. P. falciparum infections were detected on blood-smear examination in 39 participants (35.5%) who received 10 mg of CIS43LS per kilogram, 20 (18.2%) who received 40 mg of CIS43LS per kilogram, and 86 (78.2%) who received placebo. At 6 months, the efficacy of 40 mg of CIS43LS per kilogram as compared with placebo was 88.2% (adjusted 95% confidence interval [CI], 79.3 to 93.3; P<0.001), and the efficacy of 10 mg of CIS43LS per kilogram as compared with placebo was 75.0% (adjusted 95% CI, 61.0 to 84.0; P<0.001). CONCLUSIONS: CIS43LS was protective against P. falciparum infection over a 6-month malaria season in Mali without evident safety concerns. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04329104.).

NK cell-induced damage to P.falciparum-infected erythrocytes requires ligand-specific recognition and releases parasitophorous vacuoles that are phagocytosed by monocytes in the presence of immune IgG.

Natural killer (NK) cells lyse virus-infected cells and transformed cells through polarized delivery of lytic effector molecules into target cells. We have shown that NK cells lyse Plasmodium falciparum-infected red blood cells (iRBC) via antibody-dependent cellular cytotoxicity (ADCC). A high frequency of adaptive NK cells, with elevated intrinsic ADCC activity, in people chronically exposed to malaria transmission is associated with reduced parasitemia and resistance to disease. How NK cells bind to iRBC and the outcome of iRBC lysis by NK cells has not been investigated. We applied gene ablation in inducible erythrocyte precursors and antibody-blocking experiments with iRBC to demonstrate a central role of CD58 and ICAM-4 as ligands for adhesion by NK cells via CD2 and integrin αMß2, respectively. Adhesion was dependent on opsonization of iRBC by IgG. Live imaging and quantitative flow cytometry of NK-mediated ADCC toward iRBC revealed that damage to the iRBC plasma membrane preceded damage to P. falciparum within parasitophorous vacuoles (PV). PV were identified and tracked with a P.falciparum strain that expresses the PV membrane-associated protein EXP2 tagged with GFP. After NK-mediated ADCC, PV were either found inside iRBC ghosts or released intact and devoid of RBC plasma membrane. Electron microscopy images of ADCC cultures revealed tight NK-iRBC synapses and free vesicles similar in size to GFP+ PV isolated from iRBC lysates by cell sorting. The titer of IgG in plasma of malaria-exposed individuals that bound PV was two orders of magnitude higher than IgG that bound iRBC. This immune IgG stimulated efficient phagocytosis of PV by primary monocytes. The selective NK-mediated damage to iRBC, resulting in release of PV, and subsequent phagocytosis of PV by monocytes may combine for efficient killing and removal of intra-erythrocytic P.falciparum parasite. This mechanism may mitigate the inflammation and malaria symptoms during blood-stage P. falciparum infection.

Closing the Chasm: Understanding and Addressing the Anesthesia Workforce Supply and Demand Imbalance.

The imbalance in anesthesia workforce supply and demand has been exacerbated post-COVID due to a surge in demand for anesthesia care, especially in non-operating room anesthetizing sites, at a faster rate than the increase in anesthesia clinicians. The consequences of this imbalance or labor shortage compromise healthcare facilities, adversely affect the cost of care, worsen anesthesia workforce burnout, disrupt procedural and surgical schedules, and threaten academic missions and the ability to educate future anesthesiologists. In developing possible solutions, one must examine emerging trends that are affecting the anesthesia workforce, new technologies that will transform anesthesia care and the workforce, and financial considerations, including governmental payment policies. Possible practice solutions to this imbalance will require both short- and long-term multifactorial approaches that include increasing training positions and retention policies, improving capacity through innovations, leveraging technology, and addressing financial constraints.

Zinc-Induced Polymerization of Killer-Cell Ig-like Receptor into Filaments Promotes Its Inhibitory Function at Cytotoxic Immunological Synapses.

The inhibitory function of killer cell immunoglobulin-like receptors (KIR) that bind HLA-C and block activation of human natural killer (NK) cells is dependent on zinc. We report that zinc induced the assembly of soluble KIR into filamentous polymers, as detected by electron microscopy, which depolymerized after zinc chelation. Similar KIR filaments were isolated from lysates of cells treated with zinc, and membrane protrusions enriched in zinc were detected on whole cells by scanning electron microscopy and imaging mass spectrometry. Two independent mutations in the extracellular domain of KIR, away from the HLA-C binding site, impaired zinc-driven polymerization and inhibitory function. KIR filaments formed spontaneously, without the addition of zinc, at functional inhibitory immunological synapses of NK cells with HLA-C(+) cells. Adding to the recent paradigm of signal transduction through higher order molecular assemblies, zinc-induced polymerization of inhibitory KIR represents an unusual mode of signaling by a receptor at the cell surface.

Trans-endocytosis of intact IL-15Rα-IL-15 complex from presenting cells into NK cells favors signaling for proliferation.

Interleukin 15 (IL-15) is an essential cytokine for the survival and proliferation of natural killer (NK) cells. IL-15 activates signaling by the ß and common γ (γc) chain heterodimer of the IL-2 receptor through trans-presentation by cells expressing IL-15 bound to the α chain of the IL-15 receptor (IL-15Rα). We show here that membrane-associated IL-15Rα-IL-15 complexes are transferred from presenting cells to NK cells through trans-endocytosis and contribute to the phosphorylation of ribosomal protein S6 and NK cell proliferation. NK cell interaction with soluble or surface-bound IL-15Rα-IL-15 complex resulted in Stat5 phosphorylation and NK cell survival at a concentration or density of the complex much lower than required to stimulate S6 phosphorylation. Despite this efficient response, Stat5 phosphorylation was reduced after inhibition of metalloprotease-induced IL-15Rα-IL-15 shedding from trans-presenting cells, whereas S6 phosphorylation was unaffected. Conversely, inhibition of trans-endocytosis by silencing of the small GTPase TC21 or expression of a dominant-negative TC21 reduced S6 phosphorylation but not Stat5 phosphorylation. Thus, trans-endocytosis of membrane-associated IL-15Rα-IL-15 provides a mode of regulating NK cells that is not afforded to IL-2 and is distinct from activation by soluble IL-15. These results may explain the strict IL-15 dependence of NK cells and illustrate how the cellular compartment in which receptor-ligand interaction occurs can influence functional outcome.

Environmental and organizational correlates and motivations for provider-sponsored health plan ownership in the post-reform era.

BACKGROUND: The 1980s to 1990s saw many health systems in the United States enter and exit the insurance market in the form of provider-sponsored health plans (PSHPs). Reforms and value-based reimbursement methods have stimulated health care organizations to reconsider PSHP as a logical strategy. PURPOSE: The aim of this study was to examine market and organizational factors associated with PSHP ownership and motivations for engaging in PSHP after health care reforms. The resource dependence theory was used as a theoretical lens. METHODOLOGY/APPROACH: A sequential quantitative to qualitative mixed-methods design was used. The quantitative analysis examined data for 5,849 U.S. hospitals. Results were synthesized with qualitative findings from 10 semistructured interviews representing eight health systems in five states. RESULTS: Organizational and environmental characteristics were significantly associated with PSHP ownership. Hospital and payer concentration, Medicare penetration, income, unemployment rate, government, and for-profit and metro area hospitals were associated with a lower likelihood of PSHP ownership. Salaried physician arrangements, clinically integrated network membership and adoption of other risk-bearing arrangements were associated with higher odds of PSHP ownership. Interviewees described PSHP as the culmination of the journey to value-based care and as a strategy to improve patient care, compete, and diversify revenue streams. CONCLUSIONS: Both market and organizational factors are important considerations for hospitals contemplating PSHP ownership, and motivations for ownership cover a broad range of financial, competitive, strategic, and mission-based goals. PRACTICE IMPLICATIONS: Hospitals considering PSHP ownership must carefully evaluate their competitive landscapes and organizational resources to ensure optimal conditions for this strategy. PSHP ownership has high start-up costs and requires a long-term organizational commitment.

The adaptor protein Crk controls activation and inhibition of natural killer cells.

Natural killer (NK) cell inhibitory receptors recruit tyrosine phosphatases to prevent activation, induce phosphorylation and dissociation of the small adaptor Crk from cytoskeleton scaffold complexes, and maintain NK cells in a state of responsiveness to subsequent activation events. How Crk contributes to inhibition is unknown. We imaged primary NK cells over lipid bilayers carrying IgG1 Fc to stimulate CD16 and human leukocyte antigen (HLA)-E to inhibit through receptor CD94-NKG2A. HLA-E alone induced Crk phosphorylation in NKG2A(+) NK cells. At activating synapses with Fc alone, Crk was required for the movement of Fc microclusters and their ability to trigger activation signals. At inhibitory synapses, HLA-E promoted central accumulation of both Fc and phosphorylated Crk and blocked the Fc-induced buildup of F-actin. We propose a unified model for inhibitory receptor function: Crk phosphorylation prevents essential Crk-dependent activation signals and blocks F-actin network formation, thereby reducing constraints on subsequent engagement of activation receptors.

PD-1 Expression on NK Cells in Malaria-Exposed Individuals Is Associated with Diminished Natural Cytotoxicity and Enhanced Antibody-Dependent Cellular Cytotoxicity.

Natural killer (NK) cells are key effector cells of innate resistance capable of destroying tumors and virus-infected cells through cytotoxicity and rapid cytokine production. The control of NK cell responses is complex and only partially understood. PD-1 is an inhibitory receptor that regulates T cell function, but a role for PD-1 in regulating NK cell function is only beginning to emerge. Here, we investigated PD-1 expression on NK cells in children and adults in Mali in a longitudinal analysis before, during, and after infection with Plasmodium falciparum malaria. We found that NK cells transiently upregulate PD-1 expression and interleukin-6 (IL-6) production in some individuals during acute febrile malaria. Furthermore, the percentage of PD-1 expressing NK cells increases with age and cumulative malaria exposure. Consistent with this, NK cells of malaria-naive adults upregulated PD-1 following P. falciparum stimulation in vitro Additionally, functional in vitro studies revealed that PD-1 expression on NK cells is associated with diminished natural cytotoxicity but enhanced antibody-dependent cellular cytotoxicity (ADCC). These data indicate that PD-1+ NK cells expand in the context of chronic immune activation and suggest that PD-1 may contribute to skewing NK cells toward enhanced ADCC during infections such as malaria.

Emergency preparedness for infant and young child feeding in emergencies (IYCF-E): an Australian audit of emergency plans and guidance.

BACKGROUND: Australia experiences a high incidence of natural emergencies and Australian governments have committed significant investment into emergency preparedness and response. Amongst the population groups most vulnerable to emergencies are infants and young children with their vulnerability centering around their specific food and fluid needs. For this reason, the World Health Assembly has urged all member states to develop and implement infant and young child feeding in emergency (IYCF-E) plans in line with international guidance. This study aimed to determine the degree to which Australia has complied with this direction by conducting an audit of Australian emergency plans and guidance. METHODS: Australian Federal, State/Territory and a sample of Local government emergency plans and guidance were located via web searches. Documents were searched for key words to identify content dealing with the needs of infants and young children. Plans and guidance were also searched for content dealing with the needs of animals as a comparison. RESULTS: While plans and guidance contained numerous pointers to the desirability of having plans that address IYCF-E, there was a dearth of planning at all levels of government for the needs of infants and young children. Guidance related to heat waves contained information that could prove dangerous to infants. No agency at Federal or State/Territory had designated responsibility for IYCF-E or children in general. This was in stark contrast to the situation of animals for which there was widespread and comprehensive planning at all levels of government with clear designation of organisational responsibility. CONCLUSIONS: Lack of planning for IYCF-E in Australia places infants and young children at serious risk of adverse health consequences in emergencies. Australian Federal, State/Territory and Local governments need to take action to ensure that IYCF-E plans and guidance are developed and deployed in line with international standards. The pathway to successful integration of animal welfare plans provides a method for a similar integration of IYCF-E plans. Government health authorities are best placed to lead and be responsible for IYCF-E in Australia. National governments internationally should similarly take action to ensure that their youngest, most vulnerable citizens are protected in emergencies.

Limitations of Hoerl and McCormack's dual systems model of temporal consciousness.

Hoerl & McCormack's dual systems framework provides a new avenue toward the scientific investigation of temporal cognition. However, some shortcomings of the model should be considered. These issues include their reliance on a somewhat vague consideration of "systems" rather than specific computational processes. Moreover, the model does not consider the subjective nature of temporal experience or the role of consciousness in temporal cognition.

Semantic category priming from the groundside of objects shown in nontarget locations and at unpredictable times.

Previous research demonstrated that familiar objects that are suggested, but not consciously perceived, on the groundside of the contours of a figure activate their semantic category during perceptual organization, at least when the figure appears at fixation at an expected time. Here, we investigate whether evidence for such semantic activation extends to stimuli presented at unpredictable times in peripheral locations. Participants categorized words shown centrally as denoting natural or artificial objects (Experiments 1 and 2a) or positive or negative concepts (Experiment 2b). Prior to the word, two distractor silhouettes appeared above and below fixation; both depicted novel figures. On experimental trials, portions of well-known (familiar) objects were suggested on the groundside of the borders of one (Experiment 1) or both (Experiment 2a and 2b) silhouettes. In Experiment 1, reaction times were slower when targets words were preceded by experimental distractor silhouettes regardless of whether the object suggested on the groundside of their borders was in the same or a different category as the object denoted by the word. Overall slowing may have occurred because (a) semantic category access by objects suggested on the groundside of experimental distractor silhouettes was sufficient to require filtering but not category-specific priming, (b) more competition for object status slowed processing of experimental compared to control silhouettes, or (c) featural differences increased the difficulty of processing the experimental versus the control silhouettes. The use of two identical experimental silhouettes in Experiment 2a allowed a semantic category priming effect to emerge, showing that the categories of objects suggested on the groundside of silhouette borders can be activated at unpredictable times in nontarget locations and in more than one location of the visual field. Experiment 2a suggested that (a) better explains the results of Experiment 1 than (b and c). Experiment 2b further ruled out explanations (b and c) as reasons for the Experiment 1 results by showing that the same pattern is not obtained when the semantic category of the objects suggested on the groundside of the experimental silhouettes borders is not task-relevant and does not require filtering. Thus, spatial prime-target congruence and temporal certainty are not necessary for priming by objects suggested on the groundside of figures. Implications for our understanding of the complex processes involved in perceptual organization are considered.

Inhibitory receptor signaling via tyrosine phosphorylation of the adaptor Crk.

Many cellular responses, such as autoimmunity and cytotoxicity, are controlled by receptors with cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). Here, we showed that binding of inhibitory natural killer (NK) cell receptors to human leukocyte antigen (HLA) class I on target cells induced tyrosine phosphorylation of the adaptor Crk, concomitant with dephosphorylation of the guanine exchange factor Vav1. Furthermore, Crk dissociated from the guanine exchange factor C3G and bound to the tyrosine kinase c-Abl during inhibition. Membrane targeting of a tyrosine-mutated form of Crk could overcome inhibition of NK cell cytotoxicity, providing functional evidence that Crk phosphorylation contributes to inhibition. The specific phosphorylation of Crk and its dissociation from a signaling complex, observed here with two types of inhibitory receptors, expands the signaling potential of the large ITIM-receptor family and reveals an unsuspected component of the inhibitory mechanism.

NK Cell Proliferation Induced by IL-15 Transpresentation Is Negatively Regulated by Inhibitory Receptors.

IL-15 bound to the IL-15Rα-chain (IL-15Rα) is presented in trans to cells bearing the IL-2Rß-chain and common γ-chain. As IL-15 transpresentation occurs in the context of cell-to-cell contacts, it has the potential for regulation by and of other receptor-ligand interactions. In this study, human NK cells were tested for the sensitivity of IL-15 transpresentation to inhibitory receptors. Human cells expressing HLA class I ligands for inhibitory receptors KIR2DL1, KIR2DL2/3, or CD94-NKG2A were transfected with IL-15Rα. Proliferation of primary NK cells in response to transpresented IL-15 was reduced by engagement of either KIR2DL1 or KIR2DL2/3 by cognate HLA-C ligands. Inhibitory KIR-HLA-C interactions did not reduce the proliferation induced by soluble IL-15. Therefore, transpresentation of IL-15 is subject to downregulation by MHC class I-specific inhibitory receptors. Similarly, proliferation of the NKG2A(+) cell line NKL induced by IL-15 transpresentation was inhibited by HLA-E. Coengagement of inhibitory receptors, either KIR2DL1 or CD94-NKG2A, did not inhibit phosphorylation of Stat5 but inhibited selectively phosphorylation of Akt and S6 ribosomal protein. IL-15Rα was not excluded from, but was evenly distributed across, inhibitory synapses. These findings demonstrate a novel mechanism to attenuate IL-15-dependent NK cell proliferation and suggest that inhibitory NK cell receptors contribute to NK cell homeostasis.

Effects of aging on figure-ground perception: Convexity context effects and competition resolution.

We examined age-related differences in figure-ground perception by exploring the effect of age on Convexity Context Effects (CCE; Peterson & Salvagio, 2008). Experiment 1, using Peterson and Salvagio's procedure and black and white stimuli consisting of 2 to 8 alternating concave and convex regions, established that older adults exhibited reduced CCEs compared to younger adults. Experiments 2 and 3 demonstrated that this age difference was found at various stimulus durations and sizes. Experiment 4 compared CCEs obtained with achromatic stimuli, in which the alternating convex and concave regions were each all black or all white, and chromatic stimuli in which the concave regions were homogeneous in color but the convex regions varied in color. We found that the difference between CCEs measured with achromatic and colored stimuli was larger in older than in younger adults. Our results are consistent with the hypothesis that the senescent visual system is less able to resolve the competition among various perceptual interpretations of the figure-ground relations among stimulus regions.

A behavioral task sets an upper bound on the time required to access object memories before object segregation.

Traditional theories of vision assume that object segregation occurs before access to object memories. Yet, behavioral evidence shows that familiar configuration is a prior for segregation, and electrophysiological experiments demonstrate these memories are accessed rapidly. A behavioral index of the speed of access is lacking, however. Here we asked how quickly behavior is influenced by object memories that are accessed in the course of object segregation. We investigated whether access to object memories on the groundside of a border can slow behavior during a rapid categorization task. Participants viewed two silhouettes that depicted a real-world and a novel object. Their task was to saccade toward the real-world object as quickly as possible. Half of the nontarget novel objects were ambiguous in that a portion of a real-world object was suggested, but not consciously perceived, on the groundside of their borders. The rest of the nontargets were unambiguous. We tested whether saccadic reaction times were perturbed by the real-world objects suggested on the groundside of ambiguous novel silhouettes. In Experiments 1 and 2, saccadic reaction times were slowed when nontargets were ambiguous rather than unambiguous. Experiment 2 set an upper limit of 190 ms on the time required for object memories in grounds to influence behavior. Experiment 3 ruled out factors that could have produced longer latencies other than access to object memories. These results provide the first behavioral index of how quickly memories of objects suggested in grounds can influence behavior, placing the upper limit at 190 ms.

Age-related deficits in inhibition in figure-ground assignment.

We assessed age differences in the ability to resolve competition for figural status in stationary displays using small, enclosed, symmetrical silhouettes that participants classified as depicting "novel" or "familiar" shapes. The silhouettes were biased such that the inside was perceived as the shaped figure, and the outside was perceived as a shapeless ground. The critical manipulation was whether a portion of a meaningful object was suggested on the outside of the border of some of the novel silhouettes but not others (M+Ground and M-Ground novel silhouettes, respectively). This manipulation was intended to induce greater inhibitory competition for figural status from the groundside in M+Ground silhouettes than M-Ground silhouettes. In previous studies, young adults classified M+Ground silhouettes as "novel" faster than M-Ground silhouettes (Trujillo, Allen, Schnyer, & Peterson, 2010), suggesting that young adults may recruit more inhibition to resolve figure-ground when there is more competition. We replicated this effect with young adults in the present study, but older adults showed the opposite pattern and were less accurate in classifying M+Ground than M-Ground silhouettes. These results extend the evidence for inhibitory deficits in older adults to figure assignment in stationary displays. The (M+Ground - M-Ground) RT differences were evident in observers' longest responses, consistent with the hypothesis that inhibitory deficits are evident when the need for inhibition is substantial.