Anti-interleukin-6 antibody clazakizumab in late antibody-mediated kidney transplant rejection: effect on cytochrome P450 drug metabolism.

Targeting interleukin-6 (IL-6) is a promising strategy to counteract antibody-mediated rejection (ABMR). In inflammatory states, IL-6 antagonism was shown to modulate cytochrome P450 (CYP), but its impact on drug metabolism in ABMR treatment was not addressed so far. We report a sub-study of a phase 2 trial of anti-IL-6 antibody clazakizumab in late ABMR (ClinicalTrials.gov, NCT03444103). Twenty kidney transplant recipients were randomized to clazakizumab versus placebo (4-weekly doses; 12 weeks), followed by a 9-month extension where all recipients received clazakizumab. To study CYP2C19/CYP3A4 metabolism, we administered pantoprazole (20 mg intravenously) at prespecified time points. Dose-adjusted C0 levels (C0 /D ratio) of tacrolimus (n = 13) and cyclosporin A (CyA, n = 6) were monitored at 4-weekly intervals. IL-6 and C-reactive protein were not elevated at baseline, the latter was then suppressed to undetectable levels under clazakizumab. IL-6 blockade had no clinically meaningful impact on pantoprazole pharmacokinetics (area under the curve; baseline versus week 52: 3.16 [2.21-7.84] versus 4.22 [1.99-8.18] µg/ml*h, P = 0.36) or calcineurin inhibitor C0 /D ratios (tacrolimus: 1.49 [1.17-3.20] versus 1.37 [0.98-2.42] ng/ml/mg, P = 0.21; CyA: 0.69 [0.57-0.85] versus 1.08 [0.52-1.38] ng/ml/mg, P = 0.47). We conclude that IL-6 blockade in ABMR - in absence of systemic inflammation - may have no meaningful effect on CYP metabolism.

Sensitivity to major versus minor musical modes is bimodally distributed in young infants.

The difference between major and minor scales plays a central role in Western music. However, recent research using random tone sequences ("tone-scrambles") has revealed a dramatically bimodal distribution in sensitivity to this difference: 30% of listeners are near perfect in classifying major versus minor tone-scrambles; the other 70% perform near chance. Here, whether or not infants show this same pattern is investigated. The anticipatory eye-movements of thirty 6-month-old infants were monitored during trials in which the infants heard a tone-scramble whose quality (major versus minor) signalled the location (right versus left) where a subsequent visual stimulus (the target) would appear. For 33% of infants, these anticipatory eye-movements predicted target location with near perfect accuracy; for the other 67%, the anticipatory eye-movements were unrelated to the target location. In conclusion, six-month-old infants show the same distribution as adults in sensitivity to the difference between major versus minor tone-scrambles.

The impact of bilingual environments on selective attention in infancy.

Bilingualism has been observed to influence cognitive processing across the lifespan but whether bilingual environments have an effect on selective attention and attention strategies in infancy remains an unresolved question. In Study 1, infants exposed to monolingual or bilingual environments participated in an eye-tracking cueing task in which they saw centrally presented stimuli followed by a target appearing on either the left or right side of the screen. Halfway through the trials, the central stimuli reliably predicted targets' locations. In Study 2, the first half of the trials consisted of centrally presented cues that predicted targets' locations; in the second half, the cue-target location relation switched. All infants performed similarly in Study 1, but in Study 2 infants raised in bilingual, but not monolingual, environments were able to successfully update their expectations by making more correct anticipatory eye movements to the target and expressing faster reactive eye latencies toward the target in the post-switch condition. The experience of attending to a complex environment in which infants simultaneously process and contrast two languages may account for why infants raised in bilingual environments have greater attentional control than those raised in monolingual environments.

Development of spatial suppression surrounding the focus of visual attention.

In adulthood, research has demonstrated that surrounding the spatial location of attentional focus is a suppressive field, resulting from top-down attention promoting the processing of relevant stimuli and inhibiting surrounding distractors (e.g., Hopf et al., 2006). It is not fully known, however, how this phenomenon manifests during development. This is an important question since attention processes are likely even more critical in development because of their potential impact on learning and day-to-day activities. The current study examined whether spatial suppression surrounding the focus of visual attention, a predicted by-product of top-down attentional modulation, is observed in development. A wide age range separated in six incremental age levels was included, allowing for a detailed examination of potential differences in the effect of attention on visual processing across development. Participants between 12 and 27 years of age exhibited spatial suppression surrounding their focus of visual attention. Their accuracy increased as a function of the separation distance between a spatially cued (and attended) target and a second target, suggesting that a ring of suppression surrounded the attended target. Attentional surround suppression was not observed in 8- to 11-years-olds, even with a longer spatial cue presentation time, demonstrating that the lack of the effect at these ages is not due to slowed attentional feedback processes. Our findings demonstrate that top-down attentional processes exhibit functional maturity beginning around 12 years of age with continuing maturation of their expression until 17, which likely impacts education and the diagnosis of visual and cognitive clinical pathologies.

Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study).

OBJECTIVES: Determine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial. METHODS: Patients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data. RESULTS: Patients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively. CONCLUSION: Lesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy. TRIAL REGISTRATION NUMBER: NCT01493531.

Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase inhibitor: a 6 month phase 3 clinical trial and extension study.

Objective: To investigate the efficacy and safety of lesinurad, a selective uric acid reabsorption inhibitor, in a 6 month, phase 3 clinical trial and extension study. Methods: Patients with gout who cannot take a xanthine oxidase inhibitor (XOI) and have serum uric acid (sUA) ⩾6.5 mg/dl were randomized to receive oral lesinurad (400 mg daily) or placebo. The primary endpoint was the proportion of patients with sUA <6.0 mg/dl at month 6. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory data. Patients who completed the study were eligible for an open-label, uncontrolled extension study of lesinurad 400 mg monotherapy. Results: Patients (n = 214) were primarily white males (mean age 54.4 years; gout duration 11.2 years). Significantly more patients achieved the primary endpoint with lesinurad than placebo (29.9 vs 1.9%; P < 0.0001). Overall TEAE rates were higher with lesinurad (77.6 vs 65.4%); renal-related TEAEs (17.8%), renal-related serious TEAEs (4.7%) and serum creatinine elevations (1.5 times baseline, 24.3%) occurred only with lesinurad. A total of 143 patients (65 lesinurad, 78 placebo) enrolled in the extension study. Treatment with lesinurad 400 mg resulted in rapid and sustained sUA lowering that persisted for up to 18 months before the study was terminated prematurely. No new safety findings were observed in the extension. Conclusion: In patients with gout and intolerance/contraindication to XOIs, lesinurad 400 mg monotherapy demonstrated superior sUA lowering compared with placebo, with sustained effects for up to 18 months. Due to a high incidence of serum creatinine elevations and renal-related adverse events, including serious adverse events with lesinurad 400 mg, lesinurad should not be used as monotherapy. Trial registration: ClinicalTrials.gov (http://clinincaltrials.gov), NCT01508702.

Anticipatory eye movements and long-term memory in early infancy.

Advances in our understanding of long-term memory in early infancy have been made possible by studies that have used the Rovee-Collier's mobile conjugate reinforcement paradigm and its variants. One function that has been attributed to long-term memory is the formation of expectations (Rovee-Collier & Hayne, 1987); consequently, a long-term memory representation should be established during expectation formation. To examine this prediction and potentially open the door on a new paradigm for exploring infants' long-term memory, using the Visual Expectation Paradigm (Haith, Hazan, & Goodman, 1988), 3-month-old infants were trained to form an expectation for predictable color and spatial information of picture events and emit anticipatory eye movements to those events. One day later, infants' anticipatory eye movements decreased in number relative to the end of training when the predictable colors were changed but not when the spatial location of the predictable color events was changed. These findings confirm that information encoded during expectation formation are stored in long-term memory, as hypothesized by Rovee-Collier and colleagues. Further, this research suggests that eye movements are potentially viable measures of long-term memory in infancy, providing confirmatory evidence for early mnemonic processes.

Recent successes in the identification, development, and qualification of translational biomarkers: the next generation of kidney injury biomarkers.

The development of novel safety or efficacy biomarkers has increasingly been used to improve safety monitoring and minimize attrition during drug development; however, for new biomarkers, the failure rate can equal or exceed that of new chemical entities. Drug-induced kidney injury is recognized to occur throughout the drug development process, with histopathology considered to be the gold standard for preclinical toxicologic screening. Renal biomarkers used clinically are primarily biomarkers of renal function and are considered insensitive for the detection of drug-induced kidney injury during first-in-man studies, particularly for compounds known to induce renal injury in preclinical species. Recent efforts by public-private partnerships have led to unprecedented success in the identification, development, and qualification of several new translatable biomarkers of kidney injury in the rat. To optimize the chance of success in current and future biomarker efforts in preclinical species and man, selection and development of biomarkers should emphasize biological considerations including marker variability and biology in both health and disease. The research to support the qualification of novel renal safety markers for routine use in the clinical setting is currently underway, and results from this work are greatly anticipated.

Clazakizumab for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients: Phase 3 IMAGINE study rationale and design.

BACKGROUND: Chronic active antibody-mediated rejection (AMR) is a major cause of graft loss with no approved drugs for its treatment. Currently, off-label regimens are used, reflecting the high unmet need for effective therapies based on well-controlled trials. Clazakizumab is a high-affinity, humanized monoclonal antibody that binds interleukin-6 and decreases donor-specific antibody (DSA) production and inflammation. Phase 2 pilot studies of clazakizumab in kidney transplant recipients with chronic active AMR suggest modulation of DSA, stabilization of glomerular filtration rate (GFR), and a manageable safety profile. We report the design of the Phase 3 IMAGINE study (NCT03744910) to evaluate the safety and efficacy of clazakizumab for the treatment of chronic active AMR. METHODS: IMAGINE is a multicenter, double-blind trial of approximately 350 kidney transplant recipients with chronic active AMR (Banff chronic glomerulopathy [cg] >0 with concurrent positive human leukocyte antigen DSA) randomized 1:1 to receive clazakizumab or placebo (12.5 mg subcutaneous once every 4 weeks). The event-driven trial design will follow patients until 221 occurrences of all-cause graft loss are observed, defined as return to dialysis, graft nephrectomy, re-transplantation, estimated GFR (eGFR) <15 mL/min/1.73m2, or death from any cause. A surrogate for graft loss (eGFR slope) will be assessed at 1 year based on prior modeling validation. Secondary endpoints will include measures of pharmacokinetics/pharmacodynamics. Recruitment is ongoing across North America, Europe, Asia, and Australia. DISCUSSION: IMAGINE represents the first Phase 3 clinical trial investigating the safety and efficacy of clazakizumab in kidney transplant recipients with chronic active AMR, and the largest placebo-controlled trial in this patient population. This trial includes prognostic biomarker enrichment and uniquely utilizes the eGFR slope at 1 year as a surrogate endpoint for graft loss, which may accelerate the approval of a novel therapy for patients at risk of graft loss. The findings of this study will be fundamental in helping to address the unmet need for novel therapies for chronic active AMR. TRIAL REGISTRATION: ClinicalTrials.gov NCT03744910 . Registered on November 19, 2018.

Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia: A 12-Month Phase 3 Study.

BACKGROUND AND OBJECTIVES: Oral sodium zirconium cyclosilicate (formerly ZS-9) binds and removes potassium via the gastrointestinal tract. Sodium zirconium cyclosilicate-associated restoration and maintenance of normokalemia and adverse events were evaluated in a two-part, open label, phase 3 trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the correction phase, adult outpatients with plasma potassium ≥5.1 mmol/L (i-STAT Point-of-Care) received sodium zirconium cyclosilicate 10 g three times daily for 24-72 hours until normokalemic (potassium =3.5-5.0 mmol/L). Qualifying participants entered the ≤12-month maintenance phase and received sodium zirconium cyclosilicate 5 g once daily titrated to maintain normokalemia without dietary or medication restrictions. Prespecified primary end points were restoration of normal serum potassium values (3.5-5.0 mmol/L) during the correction phase and maintenance of serum potassium ≤5.1 mmol/L during the maintenance phase. Adverse events were assessed throughout. RESULTS: Of 751 participants, 746 (99%) achieved normokalemia during the correction phase (mean serum potassium =4.8 mmol/L; 95% confidence interval, 4.7 to 4.8) and entered the maintenance phase; 466 (63%) participants completed the 12-month trial. Participants were predominantly white, men, and age ≥65 years old; 74% had an eGFR<60 ml/min per 1.73 m2, and 65% used renin-angiotensin-aldosterone system inhibitors. Mean time on sodium zirconium cyclosilicate was 286 days. Mean daily sodium zirconium cyclosilicate dose was 7.2 g (SD=2.6). Over months 3-12, mean serum potassium was 4.7 mmol/L (95% confidence interval, 4.6 to 4.7); mean serum potassium values ≤5.1 and ≤5.5 mmol/L were achieved by 88% and 99% of participants, respectively. Of 483 renin-angiotensin-aldosterone system inhibitor users at baseline, 87% continued or had their dose increased; 11% discontinued. Among 263 renin-angiotensin-aldosterone system inhibitor-naïve participants, 14% initiated renin-angiotensin-aldosterone system inhibitor therapy. Overall, 489 (66%) participants experienced adverse events during the maintenance phase, and 22% experienced a serious adverse event. Of eight (1%) deaths, none were considered related to sodium zirconium cyclosilicate. Nine (1%) and 34 (5%) participants experienced serum potassium <3.0 and 3.0-3.4 mmol/L, respectively. CONCLUSIONS: After achieving normokalemia, individualized once daily sodium zirconium cyclosilicate was associated with maintenance of normokalemia without substantial renin-angiotensin-aldosterone system inhibitor changes for ≤12 months.

Contour integration by 6-month-old infants: discrimination of distinct contour shapes.

Previous research has indicated that the ability to integrate individual elements in the presence of noise is immature in 3-month-old infants. The present study extended the developmental timeline by investigating 6-month-olds' ability to integrate individual elements into whole contours through an assessment of their capability to discriminate circle and square contours constructed from oriented Gabor patches via a newly designed cueing paradigm for infants. If infants discriminate the centrally-presented contour cues, then their eye movements would correctly anticipate subsequent target presentation at a rate greater than chance. The results indicated that infants integrated the contours and discriminated the different shapes, but, consistent with past research, this ability is still fairly immature at this age, tolerating limited amount of noise.

Immunotherapy as a means to induce transplantation tolerance.

There have been several recent advances in the use of immunotherapy to induce transplantation tolerance. These include newer and safer protocols to create hematopoietic chimerism, the development of more-powerful T cell depleting antibodies, the identification of additional costimlulatory pathways as molecular targets and the identification of a role for suppressor cells in transplant tolerance.

Lesinurad Combined With Allopurinol: A Randomized, Double-Blind, Placebo-Controlled Study in Gout Patients With an Inadequate Response to Standard-of-Care Allopurinol (a US-Based Study).

OBJECTIVE: Lesinurad is a selective uric acid reabsorption inhibitor used for the treatment of gout in combination with a xanthine oxidase inhibitor. The Combining Lesinurad with Allopurinol Standard of Care in Inadequate Responders (CLEAR 1) study, a 12-month, multicenter, randomized, double-blind, placebo-controlled phase III trial, was conducted to investigate daily lesinurad (200 mg or 400 mg orally) added to allopurinol versus placebo plus allopurinol in patients with serum urate (UA) levels above a target of <6.0 mg/dl. METHODS: Patients receiving ≥300 mg of allopurinol (≥200 mg in those with moderate renal impairment) who had serum UA levels ≥6.5 mg/dl at screening and ≥2 gout flares during the previous year were studied. The primary end point was the proportion of patients achieving a serum UA level of <6.0 mg/dl at month 6. Key secondary end points were the mean gout flare rate requiring treatment (months 7-12) and the proportions of patients with complete resolution of ≥1 target tophus (month 12). Safety assessments included adverse events and laboratory data. RESULTS: The study patients (n = 603) were predominantly male and had a mean ± SD age of 51.9 ± 11.3 years, a gout duration of 11.8 ± 9.4 years, a baseline serum UA level of 6.94 ± 1.27 mg/dl, and were receiving an allopurinol dosage of 306.6 ± 59.58 mg/day. Lesinurad at doses of 200 mg or 400 mg added to allopurinol therapy significantly increased the proportions of patients who achieved serum UA target levels by month 6 as compared with those receiving allopurinol alone (54.2%, 59.2%, and 27.9%, respectively, P < 0.0001). Lesinurad was not significantly superior to allopurinol alone in terms of the secondary end points: rates of gout flares and complete resolution of tophi. Lesinurad was generally well-tolerated; the safety profile of the 200-mg dose was comparable to that of allopurinol alone, except for higher incidences of predominantly reversible elevations of serum creatinine levels. CONCLUSION: Lesinurad added to allopurinol provided benefit as compared with allopurinol alone in reducing serum UA levels and represents a new treatment option for patients needing additional urate-lowering therapy.

Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial.

OBJECTIVE: To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12-month phase III trial in patients with tophaceous gout. METHODS: Patients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate-lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5.0 mg/dl (month 6). The key secondary end point was the proportion of patients with complete resolution of ≥1 target tophus (month 12). Other end points included the percentage change in total target tophi area. Safety assessments included adverse events and laboratory data. RESULTS: Patients (n = 324) were predominantly male, with a mean age of 54.1 years. Significantly more patients achieved the serum UA target by month 6 with the addition of lesinurad 400 mg (76.1%; P < 0.0001), but not 200 mg (56.6%; P = 0.13), to the febuxostat therapy as compared with febuxostat alone (46.8%). At all other time points, significantly more patients in the lesinurad 200 mg group achieved the serum UA target. The number of patients with complete tophus resolution was not different between groups. Treatment with lesinurad (200 mg and 400 mg) plus febuxostat reduced the total target tophi area as compared with febuxostat alone (50.1% and 52.9% versus 28.3%, respectively; P < 0.05). Safety was generally comparable with that of febuxostat alone, except for higher rates of predominantly reversible elevations in the serum creatinine level, particularly with lesinurad 400 mg. CONCLUSION: Treatment with lesinurad in combination with febuxostat demonstrated superior lowering of serum UA levels as compared with febuxostat alone, with clinically relevant added effects on tophi and an acceptable safety profile with lesinurad 200 mg in patients with tophaceous gout warranting additional therapy.

Differential attentional responding in caesarean versus vaginally delivered infants.

Little is known about the role that the birth experience plays in brain and cognitive development. Recent research has suggested that birth experience influences the development of the somatosensory cortex, an area involved in spatial attention to sensory information. In this study, we explored whether differences in spatial attention would occur in infants who had different birth experiences, as occurs for caesarean versus vaginal delivery. Three-month-old infants performed either a spatial cueing task or a visual expectation task. We showed that caesarean-delivered infants' stimulus-driven, reflexive attention was slowed relative to vaginally delivered infants', whereas their cognitively driven, voluntary attention was unaffected. Thus, types of birth experience influence at least one form of infants' attention, and possibly any cognitive process that relies on spatial attention. This study also suggests that birth experience influences the initial state of brain functioning and, consequently, should be considered in our understanding of brain development.

Characterization of renal biomarkers for use in clinical trials: effect of preanalytical processing and qualification using samples from subjects with diabetes.

BACKGROUND: Identifying the potential for drug-induced kidney injury is essential for the successful research and development of new drugs. Newer and more sensitive preclinical drug-induced kidney injury biomarkers are now qualified for use in rat toxicology studies, but biomarkers for clinical studies are still undergoing qualification. The current studies investigated biomarkers in healthy volunteer (HV) urine samples with and without the addition of stabilizer as well as in urine from patients with normoalbuminuric diabetes mellitus (P-DM). METHODS: Urine samples from 20 male HV with stabilizer, 69 male HV without stabilizer, and 95 male DM without stabilizer (39 type 1 and 56 type 2) were analyzed for the following bio-markers using multiplex assays: α-1-microglobulin (A1M), ß-2-microglobulin, calbindin, clusterin, connective tissue growth factor (CTGF), creatinine, cystatin-C, glutathione S-transferase α (GSTα), kidney injury marker-1 (KIM-1), microalbumin, neutrophil gelatinase-associated lipocalin, osteopontin, Tamm-Horsfall urinary glycoprotein (THP), tissue inhibitor of metalloproteinase 1, trefoil factor 3 (TFF3), and vascular endothelial growth factor. RESULTS: CTGF and GSTα assays on nonstabilized urine were deemed nonoptimal (>50% of values below assay lower limits of quantification). "Expected values" were determined for HV with stabilizer, HV without stabilizer, and P-DM without stabilizer. There was a statistically significant difference between HV with stabilizer compared to HV without stabilizer for A1M, CTGF, GSTα, and THP. DM urine samples differed from HV (without stabilizer) for A1M CTGF, GSTα, KIM-1, microalbumin, osteopontin, and TFF3. A1M also correctly identified HV and DM with an accuracy of 89.0%. SUMMARY: These studies: 1) determined that nonstabilized urine can be used for assays under qualification; and 2) documented that A1M, CTGF, GSTα, KIM-1, microalbumin, osteopontin, and TFF3 were significantly increased in urine from P-DM. In addition, the 89.0% accuracy of A1M in distinguishing P-DM from HV may allow this biomarker to be used to monitor efficacy of potential renal protective agents.

Primacy of spatial information in guiding target selection for pursuit and saccades.

Previous studies have examined the facilitative effects of prior spatial information on target selection for saccadic eye movements. More recently, studies have shown that prior spatial information also influences target selection for smooth pursuit. However, direct comparisons of the effects of prior information on target selection for pursuit and saccades have not been made. To this end, we provided different classes of prior information and measured their effects on target selection for pursuit and saccades. In Experiment 1, we assessed the relative effects of spatial cues (indicating the target stimulus' initial location) and color cues (indicating the target stimulus' color) on eye movement latencies. In Experiment 2, we assessed the effects of motion cues (indicating the target stimulus' direction of motion) in addition to spatial cues. For both pursuit and saccades, we found that spatial cues reduced eye movement latencies more than color cues (Experiment 1). Spatial cues also reduced eye movement latencies more than motion cues (Experiment 2), even for pursuit, despite the fact that stimulus motion is essential for the generation of pursuit eye movements. These results indicate that both pursuit and saccades are affected to a greater degree by spatial information than motion or color information. We suggest that the primacy of spatial information for both pursuit and saccades reflects the importance of spatial attention in selecting the stimulus target for both eye movements.

Search asymmetry and eye movements in infants and adults.

Search asymmetry is characterized by the detection of a feature-present target amidst feature-absent distractors being efficient and unaffected by the number of distractors, whereas detection of a feature-absent target amidst feature-present distractors is typically inefficient and affected by the number of distractors. Although studies have attempted to investigate this phenomenon with infants (e.g., Adler, Inslicht, Rovee-Collier, & Gerhardstein in Infant Behavioral Development, 21, 253-272, 1998; Colombo, Mitchell, Coldren, & Atwater in Journal of Experimental Psychology: Learning, Memory and Cognition, 19, 98-109, 1990), due to methodological limitations, their findings have been unable to definitively establish the development of visual search mechanisms in infants. The present study assessed eye movements as a means to examine an asymmetry in responding to feature-present versus feature-absent targets in 3-month-olds, relative to adults. Saccade latencies to localize a target (or a distractor, as in the homogeneous conditions) were measured as infants and adults randomly viewed feature-present (R among Ps), feature-absent (P among Rs), and homogeneous (either all Rs or all Ps) arrays at set sizes of 1, 3, 5, and 8. Results indicated that neither infants' nor adults' saccade latencies to localize the target in the feature-present arrays were affected by increasing set sizes, suggesting that localization of the target was efficient. In contrast, saccade latencies to localize the target in the feature-absent arrays increased with increasing set sizes for both infants and adults, suggesting an inefficient localization. These findings indicate that infants exhibit an asymmetry consistent with that found with adults, providing support for functional bottom-up selective attention mechanisms in early infancy.