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Although the P3b component of the event-related brain potential is one of the most widely-studied components, its underlying generators are not currently well understood. Recent theories have suggested that the P3b is triggered by phasic activation of the locus-coeruleus norepinephrine (LC-NE) system, an important control center implicated in facilitating optimal task-relevant behavior. Previous research has reported strong correlations between pupil dilation and LC activity, suggesting that pupil diameter is a useful indicator for ongoing LC-NE activity. Given the strong relationship between LC activity and pupil dilation, if the P3b is driven by phasic LC activity, there should be a robust trial-to-trial relationship with the phasic pupillary dilation response (PDR). However, previous work examining relationships between concurrently recorded pupillary and P3b responses has not supported this. One possibility is that the relationship between the measures might be carried primarily by either inter-individual (i.e., between-participant) or intra-individual (i.e., within-participant) contributions to coupling, and prior work has not systematically delineated these relationships. Doing so in the current study, we do not find evidence for either inter-individual or intra-individual relationships between the PDR and P3b responses. However, baseline pupil dilation did predict the P3b. Interestingly, both the PDR and P3b independently predicted inter-individual and intra-individual variability in decision response time. Implications for the LC-P3b hypothesis are discussed.

There is an apparent disparity between the fields of cognitive audiology and cognitive electrophysiology as to how linguistic context is used when listening to perceptually challenging speech. To gain a clearer picture of how listening effort impacts context use, we conducted a pre-registered study to simultaneously examine electrophysiological, pupillometric, and behavioral responses when listening to sentences varying in contextual constraint and acoustic challenge in the same sample. Participants (N = 44) listened to sentences that were highly constraining and completed with expected or unexpected sentence-final words ("The prisoners were planning their escape/party") or were low-constraint sentences with unexpected sentence-final words ("All day she thought about the party"). Sentences were presented either in quiet or with +3 dB SNR background noise. Pupillometry and EEG were simultaneously recorded and subsequent sentence recognition and word recall were measured. While the N400 expectancy effect was diminished by noise, suggesting impaired real-time context use, we simultaneously observed a beneficial effect of constraint on subsequent recognition memory for degraded speech. Importantly, analyses of trial-to-trial coupling between pupil dilation and N400 amplitude showed that when participants' showed increased listening effort (i.e., greater pupil dilation), there was a subsequent recovery of the N400 effect, but at the same time, higher effort was related to poorer subsequent sentence recognition and word recall. Collectively, these findings suggest divergent effects of acoustic challenge and listening effort on context use: while noise impairs the rapid use of context to facilitate lexical semantic processing in general, this negative effect is attenuated when listeners show increased effort in response to noise. However, this effort-induced reliance on context for online word processing comes at the cost of poorer subsequent memory.

OBJECTIVES: Previous studies have found a positive association between having a sense of purpose in life and memory functioning in old age. We extend these findings by examining the relationships between sense of purpose, memory performance, and subjective memory beliefs over time in a large sample of adults in mid to later adulthood. METHOD: We used data from 3633 participants of the second and third wave of the MIDUS study. Cross-lagged panel analysis investigated the relationships between the variables at the two points, which were approximately 9 years apart, while controlling for gender, age, education, positive and negative affect, and self-rated health. RESULTS: Sense of purpose in life, memory performance, and subjective memory beliefs were all cross-sectionally related to each other at both times. Longitudinally, sense of purpose was a positive predictor of subjective memory beliefs. Memory performance and subjective memory beliefs positively predicted each other over time. Furthermore, all three variables showed correlated changes over time. Exploratory analyses suggest that the covariates of affect and self-rated health are possible mediators or confounders in respectively the relationship between subjective memory beliefs and later sense of purpose, and sense of purpose and later objective memory performance. CONCLUSION: Our findings underscore once more the relevance of sense of purpose in life as a predictor of positive late life functioning, as it is related to both performance-based and subjective cognitive outcomes. More work is needed to understand mechanisms underlying the purpose-memory association in order to develop and implement purpose interventions. ispartof: AGING & MENTAL HEALTH vol:25 issue:11 pages:2018-2027 ispartof: location:England status: published

To determine whether Seraph-100 (Exthera Medical Corporation, Martinez, CA) treatment provides clinical benefit for severe coronavirus disease 2019 cases that require mechanical ventilation and vasopressor support. Data sources The first two patients in the United States treated with the novel Seraph-100 device. These cases were reviewed by the Food and Drug Administration prior to granting an emergency use authorization for treatment of coronavirus disease 2019. Study selection Case series. Data extraction Vasopressor dose, mean arterial pressure, temperature, interleukin-6, C-reactive protein, and other biomarker levels were documented both before and after Seraph-100 treatments. Data synthesis Vasopressor dose, temperature, interleukin-6, and C-reactive protein levels declined after Seraph-100 treatments. Severe acute respiratory syndrome coronavirus 2 viremia was confirmed in the one patient tested and cleared by the completion of treatments. Conclusions Seraph-100 use may improve hemodynamic stability in coronavirus disease 2019 cases requiring mechanical ventilation and vasopressor support. These findings warrant future study of a larger cohort with the addition of mortality and total hospital day outcomes.

Because the risk for cognitive pathologies such as Alzheimer’s Disease increases with advancing age, there is a critical interest in understanding the pathways that promote healthy cognitive aging. In this chapter, we review an increasingly growing set of literatures highlighting the importance of personality traits in shaping trajectories of cognitive health over the adult lifespan. We consider the evidence for differential relationships between personality and a number of cognitive domains (e.g., episodic memory, executive function) and explore the role of specific personality traits as protective factors and risk factors for cognitive change in aging. We chart the pathways (e.g., activity engagement, health behaviors) through which personality impacts cognition and consider the evidence for personality as a critical factor in understanding risk for pathological cognitive impairment in older adulthood.

The cognitive, neural, and linguistic mechanisms underlying the comprehension and production of language are complex. This complexity is compounded when we consider the fact that the majority of people in the world learn, master, and switch between multiple languages. One way that we can track the complex dynamics of language use in the brain is through the direct recording of brain electrical activity. In this chapter, we review studies of human event-related brain potentials (ERPs) and their use in elucidating the mechanisms of language processing and multilingualism. First, we introduce ERPs, discussing the neural origins of the signal, methods for ERP recording, and the many benefits of ERP measures for language research. We then discuss major ERP components, stable and reliable features of the ERP signal that reflect different aspects of sensory, perceptual, and higher-order cognitive functioning, with a focus on application to language processing in both monolingual and multilingual language contexts.

Supplemental material, QJE-STD-19-396.R2-Supplementary_Materials for Literacy skill and intra-individual variability in eye-fixation durations during reading: Evidence from a diverse community-based adult sample by Brennan R Payne, Kara D Federmeier and Elizabeth AL Stine-Morrow in Quarterly Journal of Experimental Psychology

The current study reports the effects of accumulating contextual constraints on neural indices of lexico-semantic processing (i.e., effects of word frequency and orthographic neighborhood) as a function of normal aging. Event-related brain potentials were measured from a sample of older adults as they read sentences that were semantically congruent, provided only syntactic constraints (syntactic prose), or were random word strings. A linear mixed-effects modeling approach was used to probe the effects of accumulating contextual constraints on N400 responses to individual words. Like young adults in prior work, older adults exhibited a classic word position context effect on the N400 in congruent sentences, although the magnitude of the effect was reduced in older relative to younger adults. Moreover, by modeling single-word variability in N400 responses, we observed robust effects of orthographic neighborhood density that were larger in older adults than the young, and preserved effects word frequency. Importantly, in older adults, frequency effects were not modulated by accumulating contextual constraints, unlike in the young. Collectively, these findings indicate that older adults are less likely (or able) to use accumulating top-down contextual constraints, and therefore rely more strongly on bottom-up lexical features to guide semantic access of individual words during sentence comprehension.

Background/Study Context: Conceptual frameworks are analytic models at a high level of abstraction. Their operationalization can inform randomized trial design and sample size considerations.The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) conceptual framework was empirically tested using structural equation modeling (N=2,802). ACTIVE was guided by a conceptual framework for cognitive training in which proximal cognitive abilities (memory, inductive reasoning, speed of processing) mediate treatment-related improvement in primary outcomes (everyday problem-solving, difficulty with activities of daily living, everyday speed, driving difficulty), which in turn lead to improved secondary outcomes (health-related quality of life, health service utilization, mobility). Measurement models for each proximal, primary, and secondary outcome were developed and tested using baseline data. Each construct was then combined in one model to evaluate fit (RMSEA, CFI, normalized residuals of each indicator). To expand the conceptual model and potentially inform future trials, evidence of modification of structural model parameters was evaluated by age, years of education, sex, race, and self-rated health status.Preconceived measurement models for memory, reasoning, speed of processing, everyday problem-solving, instrumental activities of daily living (IADL) difficulty, everyday speed, driving difficulty, and health-related quality of life each fit well to the data (all RMSEA.05; all CFI.95). Fit of the full model was excellent (RMSEA = .038; CFI = .924). In contrast with previous findings from ACTIVE regarding who benefits from training, interaction testing revealed associations between proximal abilities and primary outcomes are stronger on average by nonwhite race, worse health, older age, and less education (p .005).Empirical data confirm the hypothesized ACTIVE conceptual model. Findings suggest that the types of people who show intervention effects on cognitive performance potentially may be different from those with the greatest chance of transfer to real-world activities.

Objectives: Careful characterization of how functional decline co-evolves with cognitive decline in older adults has yet to be well described. Most models of neurodegenerative disease postulate that cognitive decline predates and potentially leads to declines in everyday functional abilities; however, there is mounting evidence that subtle decline in instrumental activities of daily living (IADLs) may be detectable in older individuals who are still cognitively normal. Methods: The present study examines how the relationship between change in cognition and change in IADLs are best characterized among older adults who participated in the ACTIVE trial. Neuropsychological and IADL data were analyzed for 2802 older adults who were cognitively normal at study baseline and followed for up to 10 years. Results: Findings demonstrate that subtle, self-perceived difficulties in performing IADLs preceded and predicted subsequent declines on cognitive tests of memory, reasoning, and speed of processing. Conclusions: Findings are consistent with a growing body of literature suggesting that subjective changes in everyday abilities can be associated with more precipitous decline on objective cognitive measures and the development of mild cognitive impairment and dementia. (JINS, 2018, 24, 104–112)

The facilitation of word processing by sentence context reflects the interaction between the build-up of message-level semantics and lexical processing. Yet, little is known about how this effect varies through adulthood as a function of reading skill. In this study, Participants 18-64 years old with a range of literacy competence read simple sentences as their eye movements were monitored. We manipulated the predictability of a sentence-final target word, operationalized as cloze probability. First fixation durations showed an interaction between age and literacy skill, decreasing with age among more skilled readers but increasing among less skilled readers. This pattern suggests that age-related slowing may impact reading when not buffered by skill, but with continued practice, automatization of reading can continue to develop in adulthood. In absolute terms, readers were sensitive to predictability, regardless of age or literacy, in both early and later measures. Older readers showed differential contextual sensitivity in regression patterns, effects not moderated by literacy skill. Finally, comprehension performance increased with age and literacy skill, but performance among less skilled readers was especially reduced when predictability was low, suggesting that low-literacy adults (regardless of age) struggle when creating mental representations under weaker semantic constraints. Collectively, these findings suggest that aging readers (regardless of reading skill) are more sensitive to context for meaning-integration processes; that less skilled adult readers (regardless of age) depend more on a constrained semantic representation for comprehension; and that the capacity for literacy engagement enables continued development of efficient lexical processing in adult reading development. (PsycINFO Database Record

We employed self-paced reading and event-related potential measures to investigate how adults of varying literacy levels use sentence context information when reading. Community-dwelling participants read strongly and weakly constraining sentences that ended with expected or unexpected target words. Skilled readers showed N400s that were graded by the cloze probability of the targets, with larger N400s for more unexpected words. Moreover, it took these participants longer to read unexpected targets in strongly than weakly constraining sentences, suggesting a processing cost for revising predictions. Among less skilled readers, a reliable N400 difference was found between expected and unexpected targets only for the strongly constraining sentences. They also took longer when targets were unexpected, regardless of the context. These findings suggest that lower literacy readers could only immediately take advantage of strongly constraining context information to facilitate word processing and that th...

An important question in the reading literature regards the nature of the semantic information readers can extract from the parafovea (i.e., the next word in a sentence). Recent eye-tracking findings have found a semantic parafoveal preview benefit under many circumstances, and findings from event-related brain potentials (ERPs) also suggest that readers can at least detect semantic anomalies parafoveally (Barber, Van der Meij, & Kutas, Psychophysiology, 50(1), 48–59, 2013). We use ERPs to ask whether fine-grained aspects of semantic expectancy can affect the N400 elicited by a word appearing in the parafovea. In an RSVP-with-flankers paradigm, sentences were presented word by word, flanked 2° bilaterally by the previous and upcoming words. Stimuli consisted of high constraint sentences that were identical up to the target word, which could be expected, unexpected but plausible, or anomalous, as well as low constraint sentences that were always completed with the most expected ending. Findings revealed an N400 effect to the target word when it appeared in the parafovea, which was graded with respect to the target’s expectancy and congruency within the sentence context. Furthermore, when targets appeared at central fixation, this graded congruency effect was mitigated, suggesting that the semantic information gleaned from parafoveal vision functionally changes the semantic processing of those words when foveated.

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds to and is activated by collagens. DDR1 expression increases following kidney injury and accumulating evidence suggests that it contributes to the progression of injury. To this end, deletion of DDR1 is beneficial in ameliorating kidney injury induced by angiotensin infusion, unilateral ureteral obstruction, or nephrotoxic nephritis. Most of the beneficial effects observed in the DDR1-null mice are attributed to reduced inflammatory cell infiltration to the site of injury, suggesting that DDR1 plays a pro-inflammatory effect. The goal of this study was to determine whether, in addition to its pro-inflammatory effect, DDR1 plays a deleterious effect in kidney injury by directly regulating extracellular matrix production. We show that DDR1-null mice have reduced deposition of glomerular collagens I and IV as well as decreased proteinuria following the partial renal ablation model of kidney injury. Using mesangial cells isolated from DDR1-null mice, we show that these cells produce significantly less collagen compared to DDR1-null cells reconstituted with wild type DDR1. Moreover, mutagenesis analysis revealed that mutations in the collagen binding site or in the kinase domain significantly reduce DDR1-mediated collagen production. Finally, we provide evidence that blocking DDR1 kinase activity with an ATP-competitive small molecule inhibitor reduces collagen production. In conclusion, our studies indicate that the kinase activity of DDR1 plays a key role in DDR1-induced collagen synthesis and suggest that blocking collagen-mediated DDR1 activation may be beneficial in fibrotic diseases.

Recent event-related brain potential (ERP) experiments have demonstrated parafoveal N400 expectancy and congruity effects, showing that semantic information can be accessed from words in parafoveal vision (a conclusion also supported by some eye-tracking work). At the same time, it is unclear how higher-order integrative aspects of language comprehension unfold across the visual field during reading. In the current study, we recorded ERPs in a parafoveal flanker paradigm, while readers were instructed to read passively for comprehension or to judge the plausibility of sentences in which target words varied in their semantic expectancy and congruity. We directly replicated prior work showing graded N400 effects for parafoveal viewing, which are then not duplicated when the target words are processed foveally. Critically, although N400 effects were not modulated by task goals, a posteriorly distributed late positive component thought to reflect semantic integration processes was observed to semantic incongruities only in the plausibility judgment task. However, this effect was observed at a considerable delay, appearing only after words had moved into foveal vision. Our findings thus suggest that semantic access can be initiated in parafoveal vision, whereas central foveal vision may be necessary to enact higher-order (and task-dependent) integrative processing.

Motion-controlled video games in virtual environments (VEs) are physical therapy interventions for motor skill learning in children with neuromotor conditions, such as cerebral palsy. Many VEs feature complex audiovisuals designed to motivate and engage children in repetitive use; however, the value of these enhancements remains unclear. The purpose of this study was to examine the effect of a simple versus a complex VE on motor learning of a novel balance task in typically developing (TD) children and children with cerebral palsy (CP). In addition, we explored the relationship between children’s motivation, engagement and their motor learning outcomes in each VE. Twenty-seven TD children and 6 children with hemiplegic or diplegic CP participated. Participants were randomized to practice the same novel postural control task in either a simple or a complex flat-screen display VE. Motor learning was measured by an error metric per trial. Following 40 acquisition trials, children completed motivation (Intrinsic Motivation Inventory) and engagement (User Engagement Scale) measures. They returned 2–7 days later for retention and transfer tests. Children with CP had significantly greater performance errors as compared to TD children at all sessions; however, there was no difference in performance between simple and complex VE conditions at any session, nor were there any differences in engagement or motivation between conditions or groups. Lower self-reported motivation was associated with greater performance error at retention and transfer in all participants. Study results provide no evidence for an effect of VE audiovisual complexity on children’s motor learning or affective state.

Compelling evidence supports an association between the attribute of aerobic fitness and achievement scores on standardized tests of reading. However, such standardized assessments provide only a broad valuation of a complex network of language related sub-processes that contribute to reading and are heavily confounded by other attention-related processes. The present investigation sought to clarify the nature of the association between aerobic fitness and language processing in a sample of college-aged adults. Participants were bifurcated based on aerobic fitness level and on a separate day were asked to complete a lexical decision task while neuroelectric activity was recorded. Analysis of word-level language-related ERP components revealed no fitness differences. However, lower aerobically-fit individuals elicited smaller amplitude for attention-related ERP components relative to the higher aerobically-fit group. These data provide initial evidence to suggest that fitness-related differences in reading achievement may result from attentional processes rather than acting upon specific language-related processes.

Context processing in language comprehension is multifaceted and dynamic, influencing multiple stages of sensory, perceptual, and higher-order cognitive processing. A wealth of evidence supports the idea that context information is rapidly utilized to influence ongoing language processing. At the same time, our understanding of how normative aging influences context processing is a topic of considerable debate across multiple literatures. Here, we provide a detailed overview across three distinct literatures—psycholinguistics, audiology, and cognitive electrophysiology—that have examined overlapping questions surrounding how the aging process impacts the use of context information during language processing. Following, we provide an initial framework for integrating these oft-conflicting literatures and conclude with a call for interdisciplinary and multi-modal research to bridge the gap between these literatures and move toward a more complete and generalized understanding of the dynamics of context processing across the lifespan.