The purpose of this lab study was to demonstrate proof of concept for a novel Bayesian variable selection technique for predicting complex task performance. Specifically, we show results for a Bayesian variable selection technique that used the data (rather than a priori assumptions) to guide the selection of electroencephalographic (EEG) electrodes for predicting drops in performance scores after a surprise change in task demands. The sample consisted of eight young adults who completed 10 hr of training on a complex videogame across 4 days while wearing a 128-channel EEG net. Midway through Day 4, participants faced an unexpected increase in task complexity. The results indicated substantial variability across frequency ranges and time intervals in the electrodes predictive of performance. The results are discussed in terms of future research needs toward advancing statistical techniques to inform training practices for supporting trainees’ self-regulation in simulation-based training.

Abstract Dietary iron deficiency in the absence of anemia (IDNA) affects numerous people worldwide, with a wide range of negative effects on brain functioning and cognition. Although studies employing electroencephalography (EEG) have revealed a number of negative effects of IDNA in both the time- and frequency domains, to date there have been no attempts to characterize the effects of IDNA on the temporal dynamics of whole brain interactions. To address this issue, we applied multiscale entropy (MSE) analysis to resting-state EEG data collected from IDNA (n = 21) and iron sufficient (IS, n = 21) women. The MSE analysis on this data revealed that entropy was higher overall for the IS than the IDNA group, with significant differences appearing primarily at longer time scales and under right frontal and left and right parietal electrodes. These results suggest that IDNA may negatively affect long-distance interactions among brain regions and that this could conceivably be a source of diminished cognitive function and neural resilience in IDNA.

We present a new experimental paradigm intended to allow for the acquisition of the data needed for testing strong hypotheses regarding the nature of encoded representations and the real-time processing of those representations using the same set of trials. The design is motivated by two formal theories: general recognition theory (Ashby & Townsend. Psychological Review, 93, 154-179, 1986), which addresses internal representation, and systems factorial theory (Townsend & Nozawa. Journal of Mathematical Psychology, 39, 321-359. 1995), which addresses the foundational characteristics of real-time processing. We show in the results of two experiments, one with very simple and a second with more complex stimuli, that this paradigm is capable of producing data that can allow for inferences regarding both representation and processing from the same set of trials and that those two sets of inferences can be found to be coherent with one another, allowing for the potential for the results of behavioral experimentation to seriously constrain formal and computational modeling. In this sense, the work is coherent with an overarching theme in Mary Peterson's work, specifically as an application of two theory-driven approaches to questions in cognitive representation and processing.

Background: The literature on the relationships among blood iron levels, cognitive performance, and brain iron levels specific to women at the menopausal transition is ambiguous at best. The need to better understand these potential relationships in women for whom monthly blood loss (and thus iron loss) is ceasing is highlighted by iron’s accumulation in brain tissue over time, thought to be a factor in the development of neurodegenerative disease. Methods: Non-anemic women who were either low in iron or had normal iron levels for their age and race/ethnicity provided blood samples, underwent MRI scans to estimate brain iron levels, and performed a set of cognitive tasks with concurrent EEG. Results: Cognitive performance and brain dynamics were positively related to iron levels, including measures associated with oxygen transport. There were no relationships between any of the blood measures of iron and brain iron. Conclusions: Higher iron status was associated with better cognitive performance in a sample of women who were neither iron deficient nor anemic, without there being any indication that higher levels of systemic iron were related to higher levels of brain iron. Consequently, addressing low iron levels at the menopausal transition may be a candidate approach for alleviating the “brain fog” commonly experienced at menopause.

Perceptual and cognitive effort require the expenditure of brain energy, and the efficiency of that energy expenditure can vary as a function of a range of exogenous and endogenous factors. The same is true for physical work, and tools have been developed to quantify energetic efficiency in the performance of physical work. The same is not true for the study of perceptual and cognitive effort. Here we draw on two lines of research - the formal characterization of workload capacity in perception and cognition, and the study of physical work - to propose a novel measure of neurocognitive efficiency. This neurocognitive efficiency score (NES) combines reaction time data with measures on concurrently acquired electroencephalographic (EEG) data to form a ratio that can be interpreted in terms of work accomplished relative to energy expended. We consider three measures on the EEG and show that one of them - global field power (GFP) - evidences a strong relationship to measures of metabolic energy expended. We then show how the NES can provide insights into differences in perceptual performance as a function of biological state. We argue that the NES has the potential for a wide range of applications in the study of effort exerted in perception and cognition in the context of factors including (but not limited to) aging, disease, stress, and differences in levels of expertise.

Iron deficiency (ID) is the most prevalent nutrient deficiency in the world, with a growing literature documenting the negative effects of ID on perception, attention, and memory. Animal models of ID suggest that dysregulation of dopamine is responsible for the deficits in memory. However, evidence that ID affects dopamine in humans is extremely limited. We report the results of a study involving college-aged women with and without ID learning two different category structures - a rule-based and an information-integration structure - selected based on the putative differential role of dopamine in learning these two structures. ID non-anemic (IDNA) and iron-sufficient (IS) women completed 1200 learning trials for each structure. EEG was collected to assess the effects of ID on features affected by dopaminergic state: error-related negativity (ERN) and positivity (Pe), feedback-related negativity (FRN), and task-related blink rate. In addition, we examined the EEG data for dynamics distinguishing IDNA from IS women, including a measure of neural efficiency. Both groups of women were able to learn both structures. However, IDNA women were initially slower and less accurate than IS women, specifically for the rule-based structure. There were large and persistent group differences in brain dynamics and neural efficiency measures. The results are discussed with respect to the selective impact of ID on initial rule-based learning and the persistent effect of ID on dopamine signaling and energetic efficiency.

OBJECTIVES:Animal studies have suggested that dietary iron deficiency (ID) negatively affects dopamine (DA) synthesis and re-uptake, which in turn negatively affects memory and cognition. This study was intended to assess whether the pattern electroretinogram (pattern ERG) could be used as an indirect measure of DA in college-age women with and without ID by determining the extent to which features of the ERG were sensitive to iron status and were related to other indirect measures of DA. METHODS:The pattern ERG was measured in 21 iron deficient non-anemic (IDNA) and 21 iron sufficient (IS) women, who also performed a contrast detection and probabilistic selection task, both with concurrent electroencephalography (EEG). Both spontaneous and task-related blink rates were also measured. RESULTS:The implicit times of the A- and B-waves were significantly longer for the IDNA than for the IS women. Both the amplitudes and implicit times of the A- and B-waves were significantly correlated with levels of serum ferritin (sFt). Only the amplitude of the A-wave was correlated with spontaneous blink rate. It was possible to accurately identify a woman's iron status solely on the basis of the implicit time of the B-wave. Finally, the implicit times of the ERG features mediated the relationship between iron levels and accuracy in the probabilistic selection task. CONCLUSIONS:Results suggest the utility of the pattern ERG in testing the hypothesis that iron deficiency affects DA levels in humans and that this may be one of the mechanisms by which iron deficiency negatively affects cognition.

We propose an indirect measure of the efficiency of neural processing: the neural efficiency score (NES). The basis for this measure is the hazard function on the reaction time distribution from a task, h ( t ), which can be interpreted as an instantaneous measure of work being accomplished, and which has been foundational in characterizations of perceptual and cognitive workload capacity (e.g., [Townsend & Ashby, 1978][1]; [Townsend & Nozawa, 1995][2]; [Townsend & Wenger, 2004][3]). We suggest that the global field power on electroencephalographic (EEG) data ([Skrandies, 1989][4], [1990][5]) can function as a proxy for actual energy expended, and then place h ( t ) and GFP in a ratio to give a measure that can be interpreted as work accomplished relative to energy expended. To make this proposal plausible, we first need to show that the GFP can be interpreted in terms of energy expended, and we do this using previously unpublished data from an earlier study ([Wenger, DellaValle, Murray-Kolb, & Haas, 2017][6]) in which we simultaneously collected EEG and metabolic data during the performance of a cognitive task. Having shown that the GFP can be used as a proxy for energy expended, we then demonstrate the interpretability of the NES by applying it to previously unpublished data from a more recent study ([Newbolds & Wenger, 2024][7]). These outcomes suggest the potential for broad applicability of the NES and its potential for characterizing the efficiency of neural energy expenditure in the performance of perceptual and cognitive work. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-39 [2]: #ref-41 [3]: #ref-42 [4]: #ref-35 [5]: #ref-36 [6]: #ref-45 [7]: #ref-29

Electroencephalography (EEG) allows for the evaluation of real time changes in brain (electrocortical) activity during exercise. A few studies have examined changes in electrocortical activity using stationary cycling, but the findings have been mixed. Some of these studies have found increases in brain activity following exercise, while others have found decreases in brain activity following exercise. Hence, it is of importance to identify post-exercise changes in brain activity. Sixteen healthy, untrained subjects (8 males; 8 females) participated in the study. All 16 participants performed a graded exercise test (GXT) to volitional exhaustion on an upright cycle ergometer. Continuous EEG recordings were sampled before (PRE) and immediately following (IP) the GXT. Regions of interest were primarily the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and left and right motor cortex (MC). In the DLPFC, a frontal asymmetry index was also identified. There was a statistically significant increase in theta power in the DLPFC, VLPFC, and left and right MC from PRE to IP (all p < 0.05). There was also a shift towards right hemisphere asymmetry at the IP time point in the DLPFC (p < 0.05). Finally, there was an increase in alpha power from PRE to IP in the right MC (p < 0.05). EEG could prove to be an important way to measure the effects of central fatigue on brain activity before and immediately following exercise.

Abstract Background: Non-small cell lung cancer (NSCLC) is often diagnosed late with many patients (pts) not responding to first line therapy or only responding for a limited time. BNT116 is an intravenously administered uridine RNA-based lipoplex cancer vaccine comprising six mRNAs (MAGE A3, CLDN6, KK-LC-1, PRAME, MAGE A4, MAGE C1), each encoding a tumor-associated antigen (TAA) frequently expressed in NSCLC. Here, we present preliminary results from pts with advanced unresectable or metastatic NSCLC (ECOG 0-1) receiving BNT116 + docetaxel (DTX). Methods: LuCa-MERIT-1 (NCT: 05142189, EudraCT: 2021-004739-94) is a first-in-human, open label, Phase I trial to determine safety (dose limiting toxicities [DLTs]; treatment-emergent adverse events [TEAEs]) and clinical activity (RECIST v1.1) of BNT116 alone or in combinations. The cohort reported here will inform the dose of BNT116 in combination with DTX. Pts must have progressed on PD-1/PD-L1 inhibitor and a platinum-based chemotherapy. Biomarker analysis includes e.g., immunogenicity (ELISpot, n=3), cytokines (MSD, n=20), ctDNA (Avenio ctDNA Surveillance, n=~20), and PD-L1 (IHC, n=20). Results: As of 01 DEC 2023, 20 pts (median age 66 years) have received BNT116 in addition to DTX at 75 mg/m2 Q3W. The combination demonstrated a manageable safety profile. All pts experienced at least one TEAE. TEAEs ≥Grade 3/4, (incidence rate ≥10%) include neutropenia (n=10 [50%]), pneumonia (n=3 [15%]), hypertension (n=3 [15%]), lymphocyte count decreased, diarrhea, and fatigue (each n=2 [10%]). Serious TEAEs were observed in ten pts (50%), of which three were considered as related to BNT116 (Grade 3 cytokine release syndrome, Grade 3 bronchospasm, and Grade 3 pyrexia) and three were considered as related to DTX (Grade 3 diarrhea, Grade 3 rash, and Grade 4 febrile neutropenia). No DLTs within the dose confirmation period or deaths under treatment were observed. Seven of 20 pts (35%) had a partial response, 10 of 20 pts (50%) had stable disease. The objective response rate was 35% (95% CI: 15.4-59.2) and the disease control rate was 85% (95% CI: 62.1-96.8). Robust antigen-specific T-cell responses and cytokine induction were observed even with the addition of DTX and the use of prophylactic dexamethasone on Day 2 of each cycle. Conclusions: BNT116 + DTX shows encouraging antitumor activity, consistent induction of immune responses, a manageable safety profile, and no signs of additive toxicity. Updated safety and clinical activity data will be presented along with additional biomarker data. (Funded by BioNTech) Citation Format: Bala Başak Öven, David Vicente Baz, Jürgen Wolf, Ozturk Ates, Erdem Göker, Patrick Brück, Michael Wenger, Neru Munshi, Iryna Tsyhankova, Iryna Tsyhankova, Malgorzata Kaczorowska, Thomas Schell, Janet L. Markman, Huyuan Yang, Özlem Türeci, Uğur Şahin, Patrick Forde, Akin Atmaca. Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen mRNA vaccine BNT116 + docetaxel in patients with advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT051.

Background BNT116 is an intravenously administered RNA-lipoplex therapeutic cancer vaccine comprising six RNAs each encoding a tumor-associated antigen (TAA) frequently expressed in non-small cell lung cancer (NSCLC). Here, we report preliminary results from patients with advanced unresectable or metastatic NSCLC (ECOG 0–2) receiving BNT116 monotherapy with optional addition of cemiplimab. Methods LuCa-MERIT-1 is a first-in-human, open label, Phase I trial with cohorts to confirm the dose of BNT116 alone or as combination therapy with cemiplimab, docetaxel, and/or carboplatin/paclitaxel (21-day cycles). The first six BNT116 doses are administered once weekly during Cycles 1 and 2 and three-weekly from Cycle 3 onwards. The cohort reported here will confirm the dose of BNT116 as monotherapy. Cemiplimab may be added from cycle 3 if tumor samples exhibit PD-L1 expression (tumor proportion score ≥1%). Patients’ prior therapies must have included a PD-1/PD-L1 inhibitor, a platinum-based chemotherapy regimen as well as one other systemic therapy. The objectives are to determine safety (dose limiting toxicities [DLTs] in Cycle 1; treatment-emergent adverse events [TEAEs]), and clinical activity (RECIST v1.1). Tumor and blood samples will be used for biomarker analysis. Results As of 01 March 2023, 18 patients (median age 65 years) have received BNT116 in the reported cohort (n=13 monotherapy only; n=5 cemiplimab added after Cycle 3). Most (16/18 [89%]) had received ≥3 prior therapy lines. All patients experienced ≥1 TEAE, and most TEAEs were grade 1–2 (table 1). TEAEs (incidence rate ≥5%) include pyrexia (n=12 [67%], grade 1–3), chills (n=9 [50%], grade 1–2), and vomiting (n=5 [28%], grade 1–2). Pyrexia and chills were considered treatment-related TEAEs for BNT116. Serious TEAEs were observed in 5/18 (28%) patients (grade 2 pneumothorax [n=1] or pyrexia [n=1], grade 3 fatigue [n=1] or pneumonia [n=1], and grade 4 acute kidney injury [n=1]). The latter grade 4 TEAE occurred during safety follow-up after trial treatment termination and was considered as unrelated to treatment with IMP. No DLTs or deaths under treatment were observed. Ten of 18 patients were evaluable for clinical activity (n=5 monotherapy only; n=5 cemiplimab added after Cycle 3). Of these, 6/10 had stable disease and 4/10 had progressive disease. The median duration of disease control was 1.53 months. Conclusions In this trial, BNT116 was generally well tolerated with an expected safety profile as monotherapy and in combination with cemiplimab. Updated safety and clinical activity data will be presented along with additional biomarker data (TAA expression, PD-L1 expression, cytokines, tumor markers). Acknowledgements LuCa-MERIT-1 is funded by BioNTech SE. The authors would like to acknowledge Nick Fulcher and Andrew Finlayson (BioNTech SE) for medical writing support. Cemiplimab was provided by Regeneron Pharmaceuticals, Inc. Trial Registration EudraCT: 2021–004739-94, ClinicalTrials.gov: NCT05142189. Ethics Approval This study was reviewed and approved by the institutional review boards of the participating institutions.

Systems factorial theory (SFT) focuses on the real-time processing characteristics of encoded representations, allowing for strong tests of hypotheses regarding architecture (serial, parallel, coactive), stopping rule (self-terminating, exhaustive), independence in rate (dependent, independent), and capacity (limited, unlimited, super-capacity). General recognition theory (GRT) focuses on the nature of the encoded representations, allowing for tests of hypotheses regarding perceptual independence, perceptual separability, and decisional separability. For the most part, these two theories have been applied separately, in no small part because the associated experimental methodologies have been distinct. However, recent work applying both approaches with the same observers has illustrated the inferential power that accrues to the combination of methodologies. The present study investigated the potential for a new experimental paradigm to provide, on a set of single trials, the data needed to test hypotheses both about real-time processing characteristics and the nature of the encoded representation. That is a true unified GRT-SFT design. A total of six participants performed 10 sessions each of the new paradigm, the sequential categorization identification paradigm. On each trial, participants first gave a categorization decision that provided the data needed for the SFT analyses. They then gave an identification decision that provided the data needed for the GRT analyses. Feedback on the two decisions was provided only on an initial practice block. Analyses of the data indicated that the new paradigm produced data that were interpretable from both perspectives. Thus, the present study provides a proof of concept that it empirically feasible to assess all the vital characteristic associated with SFT and GRT within the same study and observers.

The retina contains numerous dopamine (DA) receptors as well as dopaminergic amacrine cells and, in animal models, the level of DA in the eye has been shown to be proportional to central DA levels. In this study, we investigated the potential for the pattern electroretinogram to be a sensitive indirect measure of central DA. This was done in the context of understanding the role of variations in DA levels as a function of variations in iron levels in women of reproductive age. Having a reliable indirect measure of DA is motivated by the invasive nature of direct measures. A total of 20 iron deficient non-anemic (IDNA) and 20 iron sufficient women (IS) were recruited and performed four visual tasks: (a) a pattern electroretinogram assessment, (b) a probabilistic selection task, (c) a contrast detection threshold task, and (d) a measure of spontaneous blink rate. Results showed that the latency but not the amplitude of the a- and b-waves of the electroretinogram varied as a function of iron status, with the latencies of both waves being longer for the IDNA than for the IS participants. In addition, contrast detection thresholds were significantly higher for the IDNA than for the IS participants. Critically, the amplitudes and latencies of the a- and b-waves were more strongly correlated with serum ferritin, the storage form of iron critical for DA synthesis and reuptake, than were either spontaneous or task-related blink rate. Finally, the latency of the a-wave was superior to spontaneous blink rate in classifying participants as either IDNA or IS. In sum, the pattern electroretinogram showed itself to be promising as an indirect measure of DA in the context of human iron deficiency.

What are the geometric and information processing characteristics of elementary figures composed of simple physical dimensions? There have been a number of investigations of perception of rectangles, including debate about configurality (e.g., integrality and gestalt properties) as well as the prime perceptual dimensions. Yet, because of ambiguity even in the "right" definition of configurality and an absence of penetrating methodologies, there is still little known concerning the information processing of these patterns. To this end, the present study brings together two separate theory-driven methodologies, general recognition theory (GRT) and systems factorial technology (SFT). The first attacks the problem of dimensional interactions while the latter seeks to uncover process characteristics such as architecture, decisional stopping rules, and workload capacity. The same observers and as much as possible, the same stimuli were used in both approaches. Through our GRT analyses, we found strong evidence for dependencies between the percepts of height and width on both within-stimulus and cross-stimulus bases. Height perception was better with narrow widths and width perception was superior with short heights. In addition, a significant positive within-trial correlation of dimensions was evidenced within squares but not with rectangles. Our SFT initiative uncovered consistent signatures of parallelism paired with super capacity, the latter appearing both through the traditional conditioning on being correct and still present when modest speed accuracy trade-off was accounted for. Thus, the SFT and GRT inferences were quite compatible with a plausible cause of the positive correlations being across-channel facilitatory interactions which led to super capacity processing.

Background: Iron deficiency is highly prevalent in South Asia, especially among women and children in Bangladesh. Declines in cognitive performance are among the many functional consequences of iron deficiency. Objective: We tested the hypothesis that, over the course of a 4-month iron fortification trial, cognitive performance would improve, and that improvement would be related to improvements in iron status. Methods: Participants included 359 adolescent girls attending Bangladesh Rural Advancement Committee (BRAC) clubs as a subsample of a larger double-blind, cluster-randomized community trial in which participants were assigned to one of three conditions: a condition in which no lentils were supplied (NL, n = 118, but which had the usual intake of lentils), a control (non-fortified) lentil condition (CL, n = 124), and an iron-fortified lentil condition (FL, n = 117). In the FL and CL conditions, approximately 200 g of cooked lentils were served five days per week for a total of 85 feeding days. In addition to biomarkers of iron status, five cognitive tasks were measured at baseline (BL) and endline (EL): simple reaction time task (SRT), go/no-go task (GNG), attentional network task (ANT), the Sternberg memory search Task (SMS), and a cued recognition task (CRT). Results: Cognitive performance at EL was significantly better for those in the FL relative to the CL and NL conditions, with this being true for at least one variable in each task, except for the GNG. In addition, there were consistent improvements in cognitive performance for those participants whose iron status improved. Although there were overall declines in iron status from BL to EL, the declines were smallest for those in the FL condition, and iron status was significantly better for those in FL condition at EL, relative to those in the CL and NL conditions. Conclusions: the provision of iron-fortified lentils provided a protective effect on iron status in the context of declines in iron status and supported higher levels of cognitive performance for adolescent girls at-risk of developing iron deficiency.

Iron deficiency (ID) and iron deficiency anemia (IDA) are highly-prevalent nutrient deficiencies and have been shown to have a range of negative effects on cognition and brain function. Human intervention studies including measures at three levels—blood, brain, and behavior—are rare and our objective was to model the relationships among measures at these three levels in school-going Indian adolescents. Male and female adolescents in rural India were screened for ID/IDA. Subjects consumed 2 meals/day for 6 months; half were randomly assigned to consume meals made from a standard grain (pearl millet) and half consumed meals made from an iron biofortified pearl millet (BPM). Prior to and then at the conclusion of the feeding trial, they completed a set of cognitive tests with concurrent electroencephalography (EEG). Overall, serum ferritin (sFt) levels improved over the course of the study. Ten of 21 possible measures of cognition showed improvements from baseline (BL) to endline (EL) that were larger for those consuming BPM than for those consuming the comparison pearl millet (CPM). Critically, the best model for the relationship between change in iron status and change in cognition had change in brain measures as a mediating factor, with both change in serum ferritin as a primary predictor and change in hemoglobin as a moderator. A dietary intervention involving a biofortified staple grain was shown to be efficacious in improving blood iron biomarkers, behavioral measures of cognition, and EEG measures of brain function. Modeling the relationships among these variables strongly suggests multiple mechanisms by which blood iron level affects brain function and cognition. Registered at ClinicalTrials.gov, NCT02152150 , 02 June 2014.