Current and next-generation formulation strategies for inactivated polio vaccines to lower costs, increase coverage, and facilitate polio eradication.

Implementation of inactivated polio vaccines (IPV) containing Sabin strains (sIPV) will further enable global polio eradication efforts by improving vaccine safety during use and containment during manufacturing. Moreover, sIPV-containing vaccines will lower costs and expand production capacity to facilitate more widespread use in low- and middle-income countries (LMICs). This review focuses on the role of vaccine formulation in these efforts including traditional Salk IPV vaccines and new sIPV-containing dosage forms. The physicochemical properties and stability profiles of poliovirus antigens are described. Formulation approaches to lower costs include developing multidose and combination vaccine formats as well as improving storage stability. Formulation strategies for dose-sparing and enhanced mucosal immunity include employing adjuvants (e.g. aluminum-salt and newer adjuvants) and/or novel delivery systems (e.g. ID administration with microneedle patches). The potential for applying these low-cost formulation development strategies to other vaccines to further improve vaccine access and coverage in LMICs is also discussed.

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material.

Formulation is critical to successful delivery of lyophilized biologics. We have compared the impact of buffer choice and the addition of sodium chloride (a formulant often viewed as unfavorable for freeze-drying applications) on the outcome of trial lyophilization of an interleukin-6 reference material. While phosphate buffer was a preferred choice and yielded well-formed cakes associated with fair recovery of biological activity, the resultant residual moisture content was high (2-4% w/w). By inclusion of isotonic levels of NaCl, the freeze-dried appearance and process were not impaired, but the residual moisture delivered was considerably reduced to levels <1% w/w. We postulate that this is due to the presence of a more open-cake structure and support this with evidence from thermal analysis and scanning electron microscopy. This work illustrates the importance of wide ranging empirical investigation of formulation options in order to optimize freeze-drying outcomes for biologics.

Protein Engineering and HDX Identify Structural Regions of G-CSF Critical to Its Stability and Aggregation.

The protein engineering and formulation of therapeutic proteins for prolonged shelf-life remain a major challenge in the biopharmaceutical industry. Understanding the influence of mutations and formulations on the protein structure and dynamics could lead to more predictive approaches to their improvement. Previous intrinsic fluorescence analysis of the chemically denatured granulocyte colony-stimulating factor (G-CSF) suggested that loop AB could subtly reorganize to form an aggregation-prone intermediate state. Hydrogen deuterium exchange mass spectrometry (HDX-MS) has also revealed that excipient binding increased the thermal unfolding transition midpoint (Tm) by stabilizing loop AB. Here, we have combined protein engineering with biophysical analyses and HDX-MS to reveal that increased exchange in a core region of the G-CSF comprising loop AB (ABI, a small helix, ABII) and loop CD packed onto helix B and the beginning of loop BC leads to a decrease in Tm and higher aggregation rates. Furthermore, some mutations can increase the population of the aggregation-prone conformation within the native ensemble, as measured by the greater local exchange within this core region.

Genetic diversity across the mitochondrial genome of eastern oysters (Crassostrea virginica) in the northern Gulf of Mexico.

The eastern oyster, Crassostrea virginica, is divided into four populations along the western North Atlantic, however, the only published mitochondrial genome sequence was assembled using one individual in Delaware. This study aimed to (1) assemble C. virginica mitochondrial genomes from Texas with pooled restriction-site-associated DNA sequencing (ezRAD), (2) evaluate the validity of the mitochondrial genome assemblies including comparison with Sanger sequencing data, and (3) evaluate genetic differentiation both between the Delaware and Texas genomes, as well as among three bays in Texas. The pooled-genome-assembled-genomes (PAGs) from Texas exhibited several characteristics indicating that they were valid, including elevated nucleotide diversity in non-coding and the third position of codons, placement as the sister haplotype of the genome from Delaware in a phylogenetic reconstruction of Crassostrea mitochondrial genomes, and a lack of genetic structure in the ND4 gene among the three Texas bays as was found with Sanger amplicons in samples from the same bays several years prior. In the comparison between the Delaware and Texas genome, 27 of 38 coding regions exhibited variability between the two populations, which were differentiated by 273 mutations, versus 1-13 mutations among the Texas samples. Using the full PAGs, there was no additional evidence for population structure among the three Texas bays. While population genetics is rapidly moving towards larger high-density datasets, studies of mitochondrial DNA (and genomes) can be particularly useful for comparing historic data prior to the modern era of genomics. As such, being able to reliably compile mitochondrial genomes from genomic data can improve the ability to compare results across studies.

Formulation Development and Improved Stability of a Combination Measles and Rubella Live-Viral Vaccine Dried for Use in the NanopatchTM Microneedle Delivery System.

Measles (Me) and rubella (Ru) viral diseases are targeted for elimination by ensuring a high level of vaccination coverage worldwide. Less costly, more convenient MeRu vaccine delivery systems should improve global vaccine coverage, especially in low - and middle - income countries (LMICs). In this work, we examine formulating a live, attenuated Me and Ru combination viral vaccine with Nanopatch™, a solid polymer micro-projection array for intradermal delivery. First, high throughput, qPCR-based viral infectivity and genome assays were established to enable formulation development to stabilize Me and Ru in a scaled-down, custom-built evaporative drying system to mimic the Nanopatch™ vaccine coating process. Second, excipient screening and optimization studies identified virus stabilizers for use during the drying process and upon storage in the dried state. Finally, a series of real-time and accelerated stability studies identified eight candidate formulations that met a target thermal stability criterion for live vaccines (<1 log10 loss after 1 week storage at 37°C). Compared to -80°C control samples, the top candidate formulations resulted in minimal viral infectivity titer losses after storage at 2-8°C for 6 months (i.e., <0.1 log10 for Me, and ~0.4 log10 for Ru). After storage at 25°C over 6 months, ~0.3-0.5 and ~1.0-1.4 log10 titer losses were observed for Me and Ru, respectively, enabling the rank-ordering of the stability of candidate formulations. These results are discussed in the context of future formulation challenges for developing microneedle-based dosage forms containing stabilized live, attenuated viral vaccines for use in LMICs.

Formulation development of a live attenuated human rotavirus (RV3-BB) vaccine candidate for use in low- and middle-income countries.

Formulation development was performed with the live, attenuated, human neonatal rotavirus vaccine candidate (RV3-BB) with three main objectives to facilitate use in low- and middle- income countries including (1) a liquid, 2-8°C stable vaccine, (2) no necessity for pre-neutralization of gastric acid prior to oral administration of a small-volume dose, and (3) a low-cost vaccine dosage form. Implementation of a high-throughput RT-qPCR viral infectivity assay for RV3-BB, which correlated well with traditional FFA assays in terms of monitoring RV3-BB stability profiles, enabled more rapid and comprehensive formulation development studies. A wide variety of different classes and types of pharmaceutical excipients were screened for their ability to stabilize RV3-BB during exposure to elevated temperatures, freeze-thaw and agitation stresses. Sucrose (50-60% w/v), PEG-3350, and a solution pH of 7.8 were selected as promising stabilizers. Using a combination of an in vitro gastric digestion model (to mimic oral delivery conditions) and accelerated storage stability studies, several buffering agents (e.g., succinate, adipate and acetate at ~200 to 400 mM) were shown to protect RV3-BB under acidic conditions, and at the same time, minimize virus destabilization during storage. Several optimized RV3-BB candidate formulations were identified based on negligible viral infectivity losses during storage at 2-8°C and -20°C for up to 12 months, as well as by relative stability comparisons at 15°C and 25°C (up to 12 and 3 months, respectively). These RV3-BB stability results are discussed in the context of stability profiles of other rotavirus serotypes as well as future RV3-BB formulation development activities.

Genetic and phenotypic variation exhibit both predictable and stochastic patterns across an intertidal fish metapopulation.

Interactions among selection, gene flow, and drift affect the trajectory of adaptive evolution. In natural populations, the direction and magnitude of these processes can be variable across different spatial, temporal, or ontogenetic scales. Consequently, variability in evolutionary processes affects the predictability or stochasticity of microevolutionary outcomes. We studied an intertidal fish, Bathygobius cocosensis (Bleeker, 1854), to understand how space, time, and life stage structure genetic and phenotypic variation in a species with potentially extensive dispersal and a complex life cycle (larval dispersal preceding benthic recruitment). We sampled juvenile and adult life stages, at three sites, over three years. Genome-wide SNPs uncovered a pattern of chaotic genetic patchiness, that is, weak-but-significant patchy spatial genetic structure that was variable through time and between life stages. Outlier locus analyses suggested that targets of spatially divergent selection were mostly temporally variable, though a significant number of spatial outlier loci were shared between life stages. Head shape, a putatively ecologically responsive (adaptive) phenotype in B. cocosensis also exhibited high temporal variability within sites. However, consistent spatial relationships between sites indicated that environmental similarities among sites may generate predictable phenotype distributions across space. Our study highlights the complex microevolutionary dynamics of marine systems, where consideration of multiple ecological dimensions can reveal both predictable and stochastic patterns in the distributions of genetic and phenotypic variation. Such considerations probably apply to species that possess short, complex life cycles, have large dispersal potential and fecundities, and that inhabit heterogeneous environments.

Effect of Formulation Variables on the Stability of a Live, Rotavirus (RV3-BB) Vaccine Candidate using in vitro Gastric Digestion Models to Mimic Oral Delivery.

In this work, two different in vitro gastric digestion models were used to evaluate the stability of a live attenuated rotavirus vaccine candidate (RV3-BB) under conditions designed to mimic oral delivery in infants. First, a forced-degradation model was established at low pH to assess the buffering capacity of formulation excipients and to screen for RV3-BB stabilizers. Second, a sequential-addition model was implemented to examine RV3-BB stability under conditions more representative of oral administration to infants. RV3-BB rapidly inactivated at < pH 5.0 (37 °C, 1 h) as measured by an infectivity RT-qPCR assay. Pre-neutralization with varying volumes of infant formula (Enfamil®) or antacid (Mylanta®) conferred partial to full protection of RV3-BB. Excipients with sufficient buffering capacity to minimize acidic pH inactivation of RV3-BB were identified (e.g., succinate, acetate, adipate), however, they concomitantly destabilized RV3-BB in accelerated storage stability studies. Both effects were concentration dependent, thus excipient optimization was required to design candidate RV3-BB formulations which minimize acid-induced viral inactivation during oral delivery while not destabilizing the vaccine during long-term 2-8 °C storage. Finally, a statistical Design -of-Experiments (DOE) study examining RV3-BB stability in the in vitro sequential-addition model identified key formulation parameters likely affecting RV3-BB stability during in vivo oral delivery.

Evidence for population genetic structure in two exploited Mekong River fishes across a natural riverine barrier.

Impacts of urban development on aquatic populations are often complex and difficult to ascertain, but population genetic analysis has allowed researchers to monitor and estimate gene flow in the context of existing and future hydroelectric projects. The Lower Mekong Basin is undergoing rapid hydroelectric development with around 50 completed and under-construction dams and 95 planned dams. The authors investigated the baseline genetic diversity of two exploited migratory fishes, the mud carp Henicorhynchus lobatus (five locations), and the rat-faced pangasiid catfish, Helicophagus leptorhynchus (two locations), in the Lower Mekong Basin using the genomic double digest restriction site-associated DNA (ddRAD) sequencing method. In both species, fish sampled upstream of Khone Falls were differentiated from those collected at other sites, and Ne estimates at the site above the falls were lower than those at other sites. This was the first study to utilize thousands of RAD-generated single nucleotide polymorphisms to indicate that the Mekong's Khone Falls are a potential barrier to gene flow for these two moderately migratory species. The recent completion of the Don Sahong dam across one of the only channels for migratory fishes through Khone Falls may further exacerbate signatures of isolation and continue to disrupt the migration patterns of regionally vital food fishes. In addition, H. lobatus populations downstream of Khone Falls, including the 3S Basin and Tonle Sap system, displayed robust connectivity. Potential obstruction of migration pathways between these river systems resulting from future dam construction may limit dispersal, which has led to elevated inbreeding rates and even local extirpation in other fragmented riverine species.

Performing Sparse Regularization and Dimension Reduction Simultaneously in Multimodal Data Fusion.

Collecting multiple modalities of neuroimaging data on the same subject is increasingly becoming the norm in clinical practice and research. Fusing multiple modalities to find related patterns is a challenge in neuroimaging analysis. Canonical correlation analysis (CCA) is commonly used as a symmetric data fusion technique to find related patterns among multiple modalities. In CCA-based data fusion, principal component analysis (PCA) is frequently applied as a preprocessing step to reduce data dimension followed by CCA on dimension-reduced data. PCA, however, does not differentiate between informative voxels from non-informative voxels in the dimension reduction step. Sparse PCA (sPCA) extends traditional PCA by adding sparse regularization that assigns zero weights to non-informative voxels. In this study, sPCA is incorporated into CCA-based fusion analysis and applied on neuroimaging data. A cross-validation method is developed and validated to optimize the parameters in sPCA. Different simulations are carried out to evaluate the improvement by introducing sparsity constraint to PCA. Four fusion methods including sPCA+CCA, PCA+CCA, parallel ICA and sparse CCA were applied on structural and functional magnetic resonance imaging data of mild cognitive impairment subjects and normal controls. Our results indicate that sPCA significantly can reduce the impact of non-informative voxels and lead to improved statistical power in uncovering disease-related patterns by a fusion analysis.

Cryptic Lineages and a Population Dammed to Incipient Extinction? Insights into the Genetic Structure of a Mekong River Catfish.

An understanding of the genetic composition of populations across management boundaries is vital to developing successful strategies for sustaining biodiversity and food resources. This is especially important in ecosystems where habitat fragmentation has altered baseline patterns of gene flow, dividing natural populations into smaller subpopulations and increasing potential loss of genetic variation through genetic drift. River systems can be highly fragmented by dams built for flow regulation and hydropower. We used reduced-representation sequencing to examine genomic patterns in an exploited catfish, Hemibagrus spilopterus, in a hotspot of biodiversity and hydropower development-the Mekong River basin. Our results revealed the presence of 2 highly divergent coexisting genetic lineages which may be cryptic species. Within the lineage with the greatest sample sizes, pairwise FST values, principal component analysis, and a STRUCTURE analysis all suggest that long-distance migration is not common across the Lower Mekong Basin, even in areas where flood-pulse hydrology has limited genetic divergence. In tributaries, effective population size estimates were at least an order of magnitude lower than in the Mekong mainstream indicating these populations may be more vulnerable to perturbations such as human-induced fragmentation. Fish isolated upstream of several dams in one tributary exhibited particularly low genetic diversity, high amounts of relatedness, and a level of inbreeding (GIS = 0.51) that has been associated with inbreeding depression in other outcrossing species. Our results highlight the importance of assessing genetic structure and diversity in riverine fisheries populations across proposed dam development sites for the preservation of these critically important resources.

Altered functional network topology correlates with clinical measures in very early-stage, drug-naïve Parkinson's disease.

INTRODUCTION: The aim of the study was to identify abnormalities of whole-brain network functional organization and their relation to clinical measures in a well-characterized, multi-site cohort of very early-stage, drug-naïve Parkinson's Disease (PD) patients. METHODS: Functional-MRI data for 16 healthy controls and 20 very early-stage, drug-naïve patients with PD were obtained from the Parkinson's Progression Markers Initiative database after controlling for strict inclusion/exclusion imaging criteria. Connectivity between regions of interest was estimated using Pearson's correlation between averaged time-series, and subsequently a connectivity matrix was obtained for each subject. These connectivity matrices were then used in an unbiased, whole-brain graph theoretical approach to investigate the functional connectome and its correlation with disease severity in very early PD. RESULTS: The current study revealed altered network topology which correlated with multiple clinical measures in very early drug-naïve PD. Decreased functional segregation and integration (both globally and locally) were evident in PD. Importantly, our results demonstrated that most of the cortical regions hypothesized to be involved early in PD manifested decreased graph theoretical measures, despite utilizing a whole-brain analytic approach that is free from prior assumptions regarding cortical region involvement. CONCLUSION: Graph theoretical investigation of very early drug-naïve PD revealed disrupted topological organization. These findings are evident in a stringently homogeneous group of very early-stage, medication-naive, and non-tremor dominant PD patients by using a whole-brain unbiased approach. These results provide an important unbiased and rigorously controlled baseline for understanding further studies of PD functional connectivity investigating response to treatment, symptom development, and disease progression.

Development of Stabilizing Formulations of a Trivalent Inactivated Poliovirus Vaccine in a Dried State for Delivery in the Nanopatch™ Microprojection Array.

The worldwide switch to inactivated polio vaccines (IPVs) is a key component of the overall strategy to achieve and maintain global polio eradication. To this end, new IPV vaccine delivery systems may enhance patient convenience and compliance. In this work, we examine Nanopatch™ (a solid, polymer microprojection array) which offers potential advantages over standard needle/syringe administration including intradermal delivery and reduced antigen doses. Using trivalent IPV (tIPV) and a purpose-built evaporative dry-down system, candidate tIPV formulations were developed to stabilize tIPV during the drying process and on storage. Identifying conditions to minimize tIPV potency losses during rehydration and potency testing was a critical first step. Various classes and types of pharmaceutical excipients (∼50 total) were then evaluated to mitigate potency losses (measured through D-antigen ELISAs for IPV1, IPV2, and IPV3) during drying and storage. Various concentrations and combinations of stabilizing additives were optimized in terms of tIPV potency retention, and 2 candidate tIPV formulations containing cyclodextrin and a reducing agent (e.g., glutathione), maintained ≥80% D-antigen potency during drying and subsequent storage for 4 weeks at 4°C, and ≥60% potency for 3 weeks at room temperature with the majority of losses occurring within the first day of storage.

A global perspective on the trophic geography of sharks.

Sharks are a diverse group of mobile predators that forage across varied spatial scales and have the potential to influence food web dynamics. The ecological consequences of recent declines in shark biomass may extend across broader geographic ranges if shark taxa display common behavioural traits. By tracking the original site of photosynthetic fixation of carbon atoms that were ultimately assimilated into muscle tissues of 5,394 sharks from 114 species, we identify globally consistent biogeographic traits in trophic interactions between sharks found in different habitats. We show that populations of shelf-dwelling sharks derive a substantial proportion of their carbon from regional pelagic sources, but contain individuals that forage within additional isotopically diverse local food webs, such as those supported by terrestrial plant sources, benthic production and macrophytes. In contrast, oceanic sharks seem to use carbon derived from between 30° and 50° of latitude. Global-scale compilations of stable isotope data combined with biogeochemical modelling generate hypotheses regarding animal behaviours that can be tested with other methodological approaches.

Genetic patterns in peripheral marine populations of the fusilier fish Caesio cuning within the Kuroshio Current.

AIM: Mayr's central-peripheral population model (CCPM) describes the marked differences between central and peripheral populations in genetic diversity, gene flow, and census size. When isolation leads to genetic divergence, these peripheral populations have high evolutionary value and can influence biogeographic patterns. In tropical marine species with pelagic larvae, powerful western-boundary currents have great potential to shape the genetic characteristics of peripheral populations at latitudinal extremes. We tested for the genetic patterns expected by the CCPM in peripheral populations that are located within the Kuroshio Current for the Indo-Pacific reef fish, Caesio cuning. METHODS: We used a panel of 2,677 SNPs generated from restriction site-associated DNA (RAD) sequencing to investigate genetic diversity, relatedness, effective population size, and spatial patterns of population connectivity from central to peripheral populations of C. cuning along the Kuroshio Current. RESULTS: Principal component and cluster analyses indicated a genetically distinct lineage at the periphery of the C. cuning species range and examination of SNPs putatively under divergent selection suggested potential for local adaptation in this region. We found signatures of isolation-by-distance and significant genetic differences between nearly all sites. Sites closest to the periphery exhibited increased within-population relatedness and decreased effective population size. MAIN CONCLUSIONS: Despite the potential for homogenizing gene flow along the Kuroshio Current, peripheral populations in C. cuning conform to the predictions of the CCPM. While oceanography, habitat availability, and dispersal ability are all likely to shape the patterns found in C. cuning across this central-peripheral junction, the impacts of genetic drift and natural selection in increasing smaller peripheral populations appear to be probable influences on the lineage divergence found in the Ryukyu Islands.

The relationship between neuropsychological tests of visuospatial function and lobar cortical thickness.

INTRODUCTION: Tests of visuospatial function are often administered in comprehensive neuropsychological evaluations. These tests are generally considered assays of parietal lobe function; however, the neural correlates of these tests, using modern imaging techniques, are not well understood. In the current study we investigated the relationship between three commonly used tests of visuospatial function and lobar cortical thickness in each hemisphere. METHOD: Data from 374 patients who underwent a neuropsychological evaluation and MRI scans in an outpatient dementia clinic were included in the analysis. We examined the relationships between cortical thickness, as assessed with Freesurfer, and performance on three tests: Judgment of Line Orientation (JoLO), Block Design (BD) from the Fourth edition of the Wechsler Adult Intelligence Scale, and Brief Visuospatial Memory Test-Revised Copy Trial (BVMT-R-C) in patients who showed overall average performance on these tasks. Using a series of multiple regression models, we assessed which lobe's overall cortical thickness best predicted test performance. RESULTS: Among the individual lobes, JoLO performance was best predicted by cortical thickness in the right temporal lobe. BD performance was best predicted by cortical thickness in the right parietal lobe, and BVMT-R-C performance was best predicted by cortical thickness in the left parietal lobe. CONCLUSIONS: Performance on constructional tests of visuospatial function appears to correspond best with underlying cortical thickness of the parietal lobes, while performance on visuospatial judgment tests appears to correspond best to temporal lobe thickness. Future research using voxel-wise and connectivity techniques and including more diverse samples will help further understanding of the regions and networks involved in visuospatial tests.

The Genomic Observatories Metadatabase (GeOMe): A new repository for field and sampling event metadata associated with genetic samples.

The Genomic Observatories Metadatabase (GeOMe, http://www.geome-db.org/) is an open access repository for geographic and ecological metadata associated with biosamples and genetic data. Whereas public databases have served as vital repositories for nucleotide sequences, they do not accession all the metadata required for ecological or evolutionary analyses. GeOMe fills this need, providing a user-friendly, web-based interface for both data contributors and data recipients. The interface allows data contributors to create a customized yet standard-compliant spreadsheet that captures the temporal and geospatial context of each biosample. These metadata are then validated and permanently linked to archived genetic data stored in the National Center for Biotechnology Information's (NCBI's) Sequence Read Archive (SRA) via unique persistent identifiers. By linking ecologically and evolutionarily relevant metadata with publicly archived sequence data in a structured manner, GeOMe sets a gold standard for data management in biodiversity science.

Simulations indicate that scores of lionfish (Pterois volitans) colonized the Atlantic Ocean.

The invasion of the western Atlantic Ocean by the Indo-Pacific red lionfish (Pterois volitans) has had devastating consequences for marine ecosystems. Estimating the number of colonizing lionfish can be useful in identifying the introduction pathway and can inform policy decisions aimed at preventing similar invasions. It is well-established that at least ten lionfish were initially introduced. However, that estimate has not faced probabilistic scrutiny and is based solely on the number of haplotypes in the maternally-inherited mitochondrial control region. To rigorously estimate the number of lionfish that were introduced, we used a forward-time, Wright-Fisher, population genetic model in concert with a demographic, life-history model to simulate the invasion across a range of source population sizes and colonizing population fecundities. Assuming a balanced sex ratio and no Allee effects, the simulations indicate that the Atlantic population was founded by 118 (54-514, 95% HPD) lionfish from the Indo-Pacific, the Caribbean by 84 (22-328, 95% HPD) lionfish from the Atlantic, and the Gulf of Mexico by at least 114 (no upper bound on 95% HPD) lionfish from the Caribbean. Increasing the size, and therefore diversity, of the Indo-Pacific source population and fecundity of the founding population caused the number of colonists to decrease, but with rapidly diminishing returns. When the simulation was parameterized to minimize the number of colonists (high θ and relative fecundity), 96 (48-216, 95% HPD) colonists were most likely. In a more realistic scenario with Allee effects (e.g., 50% reduction in fecundity) plaguing the colonists, the most likely number of lionfish increased to 272 (106-950, 95% HPD). These results, in combination with other published data, support the hypothesis that lionfish were introduced to the Atlantic via the aquarium trade, rather than shipping. When building the model employed here, we made assumptions that minimize the number of colonists, such as the lionfish being introduced in a single event. While we conservatively modelled the introduction pathway as a single release of lionfish in one location, it is more likely that a combination of smaller and larger releases from a variety of aquarium trade stakeholders occurred near Miami, Florida, which could have led to even larger numbers of colonists than simulated here. Efforts to prevent future invasions via the aquarium trade should focus on the education of stakeholders and the prohibition of release, with adequate rewards for compliance and penalties for violations.

FN400 and LPC memory effects for concrete and abstract words.

According to dual-process models, recognition memory depends on two neurocognitive mechanisms: familiarity, which has been linked to the frontal N400 (FN400) effect in studies using ERPs, and recollection, which is reflected by changes in the late positive complex (LPC). Recently, there has been some debate over the relationship between FN400 familiarity effects and N400 semantic effects. According to one view, these effects are one and the same. Proponents of this view have suggested that the frontal distribution of the FN400 could be due to stimulus concreteness: recognition memory experiments commonly use highly imageable or concrete words (or pictures), which elicit semantic ERPs with a frontal distribution. In the present study, we tested this claim using a recognition memory paradigm in which subjects memorized concrete and abstract nouns; half of the words changed font color between study and test. FN400 and LPC old/new effects were observed for abstract as well as concrete words, and were stronger over right hemisphere electrodes for concrete words. However, there was no difference in anteriority of the FN400 effect for the two word types. These findings challenge the notion that the frontal distribution of the FN400 old/new effect is fully explained by stimulus concreteness.