Dynamic Adjustments of Cognitive Control in Healthy Aging: A Diffusion Model Analysis

The control of attention over salient yet irrelevant information is a critical component of goal-directed behavior. Compared to younger adults, older adults often produce larger interference effects in tasks which tap selective attention, a deficit that has typically been viewed as reflecting an age-related decline in attentional control processes. Interference in distinct, attentionally demanding tasks has produced different influences on the characteristics of underlying response time distributions leading to the assumption of different control mechanisms operating across various paradigms. More recently, accumulating research has shown that the magnitude of observed interference can be critically modulated by the congruency of the immediately preceding trial, a phenomenon known as the congruency sequence effect (CSE). This effect is thought to reflect the online modulation of control processes across adjacent trials. Three specific questions regarding the nature of cross-trial effects in attentional control tasks were addressed across three different experiments. First, what stimuli characteristics drive cross-trial changes in attentional control? Second, what component of cognitive processing is responsible for such changes? Third, how do these processes change as a function of healthy aging? To address these questions, Experiment 1 tested younger and older adults on versions of three attention tasks, Stroop, Simon and flanker, which were designed to eliminate common confounds such as the exact repetition of stimuli across adjacent trials. The results revealed a significant CSE was present in all tasks which was further moderated by age in two. Specifically, the CSE was larger for older adults compared to younger in the Stroop task, but smaller in the Simon task (and trending smaller in flanker). Furthermore, examination of the response time distributions indicated the CSE in Stroop was due to changes in distributional skewing whereas changes in Simon and flanker were better characterized by a simple shift. Experiment 2 was modeled closely after Experiment 1 with the addition of a response deadline procedure. This was implemented to increase the error rates in each task to better allow for the application of computational modeling (i.e., using the diffusion model). The procedure was successful in speeding up responses equally for each age group and also produced more errors, especially for younger adults. Examination of diffusion model parameters showed intriguing task dissociations such that the previous trial influenced both the non-decision time and drift rate parameters of the diffusion model in Simon but influenced primarily drift rate in both Stroop and flanker. These parameter changes were largely similar across younger and older adults Experiment 3 was designed to further probe the characteristics of stimuli that prompt cross-trial changes in control. Stroop stimuli were utilized that were either mostly congruent at the item level (i.e., the word appeared in the corresponding color most of the time), mostly incongruent (the word appeared in a non-corresponding color most of the time), or neutral (items were 50% congruent), while keeping the overall list-wide congruency constant at 50%. This manipulation (the item-specific proportion congruency effect: ISPC) has well-established effects on overall interference such that effects are smaller for the mostly incongruent items. This experiment assessed whether the differential change in conflict would produce CSEs of varying magnitude. This hypothesis was not supported as evidence was obtained for both a robust CSE and ISPC which did not interact in either younger or older adults

Combining Attentional Control and Semantic Memory Retrieval: A Sensitive Marker for Early Stage AD and AD-related Biomarkers in Healthy Older Adults

Past studies have shown that measures of attentional control and semantic memory retrieval are sensitive markers of Alzheimer disease: AD). The present study examined the utility of combining measures of attentional control and semantic retrieval within a single task to discriminate healthy aging from early stage AD and show sensitivity to AD biomarkers in healthy control individuals. On each trial of the present task, participants viewed a category: e.g. “a unit of time”) and verified whether a subsequent target item was an exemplar of the category: “hour”) or not: “clock”). Importantly, the nonmembers of the category were associatively related: e.g., a “clock” is not “a unit of time”, but is highly related), and hence, placed a premium on attentional control systems to reject. Results indicated that accuracy to the foil items was the strongest discriminator between healthy aging and very mild AD. Furthermore, accuracy correlated significantly with AD biomarkers, including tau, p-tau, Aβ42 and PIB, in healthy control participants who are at increased risk for developing Alzheimer disease. Discussion focuses on the combined influence of attentional control with explicit retrieval from semantic memory as a marker of early stage AD as well as a sensitive correlate of established biomarkers for AD risk in healthy control participants

Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.

Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome