Minimal reporting guideline for research involving eye tracking (2023 edition).

A guideline is proposed that comprises the minimum items to be reported in research studies involving an eye tracker and human or non-human primate participant(s). This guideline was developed over a 3-year period using a consensus-based process via an open invitation to the international eye tracking community. This guideline will be reviewed at maximum intervals of 4 years.

Antisaccade error rates and gap effects in psychosis syndromes from bipolar-schizophrenia network for intermediate phenotypes 2 (B-SNIP2).

BACKGROUND: Antisaccade tasks can be used to index cognitive control processes, e.g. attention, behavioral inhibition, working memory, and goal maintenance in people with brain disorders. Though diagnoses of schizophrenia (SZ), schizoaffective (SAD), and bipolar I with psychosis (BDP) are typically considered to be distinct entities, previous work shows patterns of cognitive deficits differing in degree, rather than in kind, across these syndromes. METHODS: Large samples of individuals with psychotic disorders were recruited through the Bipolar-Schizophrenia Network on Intermediate Phenotypes 2 (B-SNIP2) study. Anti- and pro-saccade task performances were evaluated in 189 people with SZ, 185 people with SAD, 96 people with BDP, and 279 healthy comparison participants. Logistic functions were fitted to each group's antisaccade speed-performance tradeoff patterns. RESULTS: Psychosis groups had higher antisaccade error rates than the healthy group, with SZ and SAD participants committing 2 times as many errors, and BDP participants committing 1.5 times as many errors. Latencies on correctly performed antisaccade trials in SZ and SAD were longer than in healthy participants, although error trial latencies were preserved. Parameters of speed-performance tradeoff functions indicated that compared to the healthy group, SZ and SAD groups had optimal performance characterized by more errors, as well as less benefit from prolonged response latencies. Prosaccade metrics did not differ between groups. CONCLUSIONS: With basic prosaccade mechanisms intact, the higher speed-performance tradeoff cost for antisaccade performance in psychosis cases indicates a deficit that is specific to the higher-order cognitive aspects of saccade generation.

Reduced white matter microstructure in bipolar disorder with and without psychosis.

OBJECTIVES: Affective and psychotic features overlap considerably in bipolar I disorder, complicating efforts to determine its etiology and develop targeted treatments. In order to clarify whether mechanisms are similar or divergent for bipolar disorder with psychosis (BDP) and bipolar disorder with no psychosis (BDNP), neurobiological profiles for both the groups must first be established. This study examines white matter structure in the BDP and BDNP groups, in an effort to identify portions of white matter that may differ between the bipolar and healthy groups or between the bipolar subgroups themselves. METHODS: Diffusion-weighted imaging data were acquired from participants with BDP (n = 45), BDNP (n = 40), and healthy comparisons (HC) (n = 66). Fractional anisotropy (FA), radial diffusivity (RD), and spin distribution function (SDF) values indexing white matter diffusivity or spin density were calculated and compared between the groups. RESULTS: In comparisons between both the bipolar groups and HC, FA (FDR < 0.00001) and RD (FDR = 0.0037) differed minimally, in localized portions of the left cingulum and corpus callosum, while reductions in SDF (FDR = 0.0002) were more widespread. The bipolar subgroups did not differ from each other on FA, RD, or SDF metrics. CONCLUSIONS: Together, these results demonstrate a novel profile of white matter differences in bipolar disorder and suggest that this white matter pathology is associated with the affective disturbance common to those with bipolar disorder rather than the psychotic features unique to some. The white matter alterations identified in this study may provide substrates for future studies examining specific mechanisms that target affective domains of illness.

Exploring Explicit Learning Strategies: A Dissociative Framework for Research.

To explain learning, comparative researchers invoke an associative construct by which immediate reinforcement strengthens animal's adaptive responses. In contrast, cognitive researchers freely acknowledge humans' explicit-learning capability to test and confirm hypotheses even lacking direct reinforcement. We describe a new dissociative framework that may stretch animals' learning toward the explicit pole of cognition. We discuss the neuroscience of reinforcement-based learning and suggest the possibility of disabling a dominant form of reinforcement-based discrimination learning. In that vacuum, researchers may have an opportunity to observe animals' explicit learning strategies (i.e., hypotheses, rules, task self-construals). We review initial research using this framework showing explicit learning by humans and perhaps by monkeys. Finally, we consider why complementary explicit and reinforcement-based learning systems might promote evolutionary and ecological fitness. Illuminating the evolution of parallel learning systems may also tell part of the story of the emergence of humans' extraordinary capacity for explicit-declarative cognition.

Breaking the perceptual-conceptual barrier: Relational matching and working memory.

Cognitive, comparative, and developmental psychologists have long been interested in humans' and animals' ability to respond to abstract relations, as this ability may underlie important capacities like analogical reasoning. Cross-species research has used relational matching-to-sample (RMTS) tasks in which participants try to find stimulus pairs that "match" because they both express the same abstract relation (same or different). Researchers seek to understand the cognitive processes that underlie successful matching performance. In the present RMTS paradigm, the abstract-relational cue was made redundant with a first-order perceptual cue. Then the perceptual cue faded, requiring participants to transition from a perceptual to a conceptual approach by realizing the task's abstract-relational affordance. We studied participants' ability to make this transition with and without a working-memory load. The concurrent load caused participants to fail to break the perceptual-conceptual barrier unless the load was abandoned. We conclude that finding the conceptual solution depends on reconstruing the task using cognitive processes that are especially reliant on working memory. Our data provide the closest existing look at this cognitive reorganization. They raise important theoretical issues for cross-species comparisons of relational cognition, especially regarding animals' limitations in this domain.

Efficacy and safety of incobotulinumtoxin A for the correction of glabellar lines among patients with skin types IV to VI.

BACKGROUND: Despite the frequent use of botulinumtoxin A (BoNTA) in non-Caucasian patients, safety and efficacy has not been well characterized in persons with darker skin. OBJECTIVE: To investigate the efficacy and safety of incobotulinumtoxin A [Xeomin® (XEO)] for the correction of glabellar lines among non-Caucasian patients with Fitzpatrick skin types IV to VI. METHODS: This open-label, single-center, post-marketing study treated 29 patients with Fitzpatrick skin types IV to VI with moderate to severe glabellar frown lines. Evaluation at day 0 included standardized photographs and patient and investigator assessments. Post evaluation, XEO was administered at 5 intramuscular injection sites with equal aliquots of 4 units per 0.1 mL. Photographs and assessments were repeated at days 30 and 90. RESULTS: Response to treatment was defined as a 1 or more point improvement in patient and investigator assessments. At day 30, 100% (n = 29; 95 C.I. 0.87, 1.00; P< .001) responded to treatment. At day 90, 69% (n=20; 95% C.I. 0.52, 0.83; P= .42) responded to treatment. The safety profile was similar to previously reported trials with BoNTA. CONCLUSION: The efficacy and safety of XEO among patients with skin types IV to VI is similar to that among persons with fairer skin.

Eco-evolutionary Guided Pathomic Analysis to Predict DCIS Upstaging.

Cancers evolve in a dynamic ecosystem. Thus, characterizing cancer's ecological dynamics is crucial to understanding cancer evolution and can lead to discovering novel biomarkers to predict disease progression. Ductal carcinoma in situ (DCIS) is an early-stage breast cancer characterized by abnormal epithelial cell growth confined within the milk ducts. Although there has been extensive research on genetic and epigenetic causes of breast carcinogenesis, none of these studies have successfully identified a biomarker for the progression and/or upstaging of DCIS. In this study, we show that ecological habitat analysis of hypoxia and acidosis biomarkers can significantly improve prediction of DCIS upstaging. First, we developed a novel eco-evolutionary designed approach to define habitats in the tumor intra-ductal microenvironment based on oxygen diffusion distance in our DCIS cohort of 84 patients. Then, we identify cancer cells with metabolic phenotypes attributed to their habitat conditions, such as the expression of CA9 indicating hypoxia responding phenotype, and LAMP2b indicating a hypoxia-induced acid adaptation. Traditionally these markers have shown limited predictive capabilities for DCIS upstaging, if any. However, when analyzed from an ecological perspective, their power to differentiate between indolent and upstaged DCIS increased significantly. Second, using eco-evolutionary guided computational and digital pathology techniques, we discovered distinct spatial patterns of these biomarkers and used the distribution of such patterns to predict patient upstaging. The patterns were characterized by both cellular features and spatial features. With a 5-fold validation on the biopsy cohort, we trained a random forest classifier to achieve the area under curve(AUC) of 0.74. Our results affirm the importance of using eco-evolutionary-designed approaches in biomarkers discovery studies in the era of digital pathology by demonstrating the role of eco-evolution dynamics in predicting cancer progression.

Engineering programmable material-to-cell pathways via synthetic notch receptors to spatially control differentiation in multicellular constructs.

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues.

Recognition of skin cancer and sun protective behaviors in skin of color.

Sun protective behaviors are not as frequently practiced in skin of color as they are amongst Caucasians.1 Thus providing a reasonable assumption this behavior, or lack thereof, increases the risk of skin cancer in this skin of color populations. The aim of this study was two-fold-- the first was to understand whether patients with skin of color, when categorized by ethnicity or skin type, are able to recognize skin cancer lesions. The second was to examine the correlation between ethnicity and/or skin type and practice of sun protective behaviors. We surveyed 105 respondents presenting for various skin problems in a dermatology office in Chicago, IL. Topics covered in the survey included recognition of skin cancer appearance and choice of sun protective behaviors. We show that there is a tendency for patients to potentially recognize atypical pigmented lesions when they are "dark moles with irregular borders" or "new moles". In contrast, there is a reduced ability among darkly pigmented skin types IV to VI, to recognize non-melanoma skin cancers. We also show that in addition to ethnicity, skin type within ethnic groups may also play an influential role on the decision to protect or not protect oneself from the sun.

Characterization of Resting-State Functional Connectivity Changes in Hypertension by a Modified Difference Degree Test.

Introduction: Hypertension affects over a billion people worldwide, and the application of neuroimaging may elucidate changes brought about by the disease. We have applied a graph theory approach to examine the organizational differences in resting-state functional magnetic resonance imaging (rs-fMRI) data between hypertensive and normotensive participants. To detect these groupwise differences, we performed statistical testing using a modified difference degree test (DDT). Methods: Structural and rs-fMRI data were collected from a cohort of 52 total (29 hypertensive and 23 normotensive) participants. Functional connectivity maps were obtained by partial correlation analysis of participant rs-fMRI data. We modified the DDT null generation algorithm and validated the change through different simulation schemes and then applied this modified DDT to our experimental data. Results: Through a comparative analysis, the modified DDT showed higher true positivity rates (TPR) when compared with the base DDT while also maintaining false positivity rates below the nominal value of 5% in nearly all analytically thresholded trials. Applying the modified DDT to our rs-fMRI data showed differential organization in the hypertension group in the regions throughout the brain including the default mode network. These experimental findings agree with previous studies. Conclusions: While our findings agree with previous studies, the experimental results presented require more investigation to prove their link to hypertension. Meanwhile, our modification to the DDT results in higher accuracy and an increased ability to discern groupwise differences in rs-fMRI data. We expect this to be useful in studying groupwise organizational differences in future studies.

Engineering Programmable Material-To-Cell Pathways Via Synthetic Notch Receptors To Spatially Control Cellular Phenotypes In Multi-Cellular Constructs.

Synthetic Notch (synNotch) receptors are modular synthetic components that are genetically engineered into mammalian cells to detect signals presented by neighboring cells and respond by activating prescribed transcriptional programs. To date, synNotch has been used to program therapeutic cells and pattern morphogenesis in multicellular systems. However, cell-presented ligands have limited versatility for applications that require spatial precision, such as tissue engineering. To address this, we developed a suite of materials to activate synNotch receptors and serve as generalizable platforms for generating user-defined material-to-cell signaling pathways. First, we demonstrate that synNotch ligands, such as GFP, can be conjugated to cell- generated ECM proteins via genetic engineering of fibronectin produced by fibroblasts. We then used enzymatic or click chemistry to covalently link synNotch ligands to gelatin polymers to activate synNotch receptors in cells grown on or within a hydrogel. To achieve microscale control over synNotch activation in cell monolayers, we microcontact printed synNotch ligands onto a surface. We also patterned tissues comprising cells with up to three distinct phenotypes by engineering cells with two distinct synthetic pathways and culturing them on surfaces microfluidically patterned with two synNotch ligands. We showcase this technology by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined spatial patterns towards the engineering of muscle tissue with prescribed vascular networks. Collectively, this suite of approaches extends the synNotch toolkit and provides novel avenues for spatially controlling cellular phenotypes in mammalian multicellular systems, with many broad applications in developmental biology, synthetic morphogenesis, human tissue modeling, and regenerative medicine.

The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice.

Background: The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information to the body and synchronize cell and tissue level rhythms and hormone release. Specific subpopulations of SCN neurons, defined by their peptide expression, regulate defined SCN output. Here we focus on the vasoactive intestinal peptide (VIP) expressing neurons of the SCN. SCN VIP neurons are known to regulate circadian rhythms and reproductive function. Methods: To specifically study SCN VIP neurons, we generated a novel knock out mouse line by conditionally deleting the SCN enriched transcription factor, Ventral Anterior Homeobox 1 (Vax1), in VIP neurons (Vax1Vip; Vax1fl/fl:VipCre). Results: We found that Vax1Vip females presented with lengthened estrous cycles, reduced circulating estrogen, and increased depressive-like behavior. Further, Vax1Vip males and females presented with a shortened circadian period in locomotor activity and ex vivo SCN circadian period. On a molecular level, the shortening of the SCN period was driven, at least partially, by a direct regulatory role of VAX1 on the circadian clock genes Bmal1 and Per2. Interestingly, Vax1Vip females presented with increased expression of arginine vasopressin (Avp) in the paraventricular nucleus, which resulted in increased circulating corticosterone. SCN VIP and AVP neurons regulate the reproductive gonadotropin-releasing hormone (GnRH) and kisspeptin neurons. To determine how the reproductive neuroendocrine network was impacted in Vax1Vip mice, we assessed GnRH sensitivity to a kisspeptin challenge in vivo. We found that GnRH neurons in Vax1Vip females, but not males, had an increased sensitivity to kisspeptin, leading to increased luteinizing hormone release. Interestingly, Vax1Vip males showed a small, but significant increase in total sperm and a modest delay in pubertal onset. Both male and female Vax1Vip mice were fertile and generated litters comparable in size and frequency to controls. Conclusion: Together, these data identify VAX1 in SCN VIP neurons as a neurological overlap between circadian timekeeping, female reproduction, and depressive-like symptoms in mice, and provide novel insight into the role of SCN VIP neurons.

Conceptual anchoring dissociates implicit and explicit category learning.

Categorization researchers have long debated the possibility of multiple category-learning systems. The need persists for paradigms that dissociate explicit-declarative category-learning processes (featuring verbalizable category rules) from implicit-procedural processes (featuring stimulus-response associations lying beneath declarative cognition). The authors contribute a new paradigm, using perfectly matched exclusive-or (XOR) category tasks differing only in the availability or absence of easily verbalizable conceptual content. This manipulation transformed learning. The conceptual task alone was learned suddenly, by insightful rule discovery, producing explicit-declarative XOR knowledge. The perceptual task was learned more gradually, consistent with associative-learning processes, producing impoverished declarative knowledge. We also tested participants under regimens of immediate and deferred reinforcement. The conceptual task alone was learned through processes that survive the loss of trial-by-trial reinforcement. All results support the idea that humans have perceptual-associative processes for implicit learning, but also an overlain conceptual system that under the right circumstances constitutes a parallel explicit-declarative category-learning system. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Joint estimation and regularized aggregation of brain network in FMRI data.

BACKGROUND: In the Gaussian graphical model framework, precision matrices reveal conditional dependence structure among random variables. In functional magnetic resonance imaging (fMRI) data, estimating such precision matrices of multi-subjects and aggregating them to a group-level is an essential step for constructing a group brain network. NEW METHOD: In this article, we considered joint estimation of multiple precision matrices with regularized aggregation. Also, in the construction of a group precision matrix, we integrated robust aggregation to the estimation. In the estimation of individual precision matrices, we took a regularization approach to induce sparsity, which made brain network estimation more realistic. RESULTS: We demonstrated the effectiveness of the proposed method through simulated examples, and analyses on real fMRI data acquired during eye movement tasks assessing cognitive control. For the fMRI data, the joint estimation of multiple precision matrices (JEMP) with regularized aggregation (RA) captured more robust associations between task-relevant neural regions of interest (ROIs), compared to the analyses using JEMP alone. The JEMP with RA also was sensitive to increased neural efficiency after task practice. COMPARISON WITH EXISTING METHOD(S): The simple average of individual precision matrices may be affected by outliers and provide inconsistent outcomes between subject-level and group-level networks. In contrast, the proposed method yielded a robust group graph that could identify and ease the effect of outliers. CONCLUSIONS: The proposed method identified regions of practice-induced attenuation associated with reduced cognitive demand after repeat task exposure. Through simulated and real data, we demonstrated that this method does not require any distribution assumption, can identify outliers, and provides robust, representative group brain networks. This method can be applied to datasets that have extensive variability and/or multiple outliers, including applications to specific, and general, cognitive processes, as well as for studies that may require longitudinal data, such as pharmaceutical trials.

Launch! Self-agency as a discriminative cue for humans (Homo sapiens) and monkeys (Macaca Mulatta).

Self-agency is a crucial aspect of self-awareness. It is underresearched given the phenomenon's subjectivity and difficulty of study. It is particularly underresearched comparatively, given that animals cannot receive agency instructions or make agency declarations. Accordingly, we developed a distinctively new self-agency paradigm. Humans and rhesus macaques learned event categories differentiated by whether the participant's volitional response controlled a screen launch. They learned by trial and error after minimal instructions with no agency orientation (humans) or no instructions (monkeys). After learning, humans' verbalized category descriptions were coded for self-agency attributions. Across three experiments, humans' agency attributions qualitatively improved discrimination performance-participants not invoking self-agency rarely exceeded chance performance. It also produced a diagnostic latency profile: classification accuracy depended heavily on the temporal relationship between the button-press and the launch, but only for those invoking agency. In our last experiment, monkeys performed the launch task. Their performance and latency profiles mirrored that of humans. Thus, self-agency can be self-discovered as a frame organizing discrimination. And it may be used as a discrimination cue by some nonhuman animals as well. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Monkeys (Macaca mulatta) learn two-choice discriminations under displaced reinforcement.

To explain animal learning, researchers invoke a dominant associative construct. In contrast, researchers freely acknowledge humans' explicit-declarative learning capacity. Here, we stretched animals' learning performance toward the explicit pole of cognition. We tested four macaques (Macaca mulatta) in new discrimination-learning paradigms. Monkeys learned a series of two-choice discrimination tasks. But immediate reinforcement was denied. Instead, reinforcement was lagged-monkeys received feedback for trial N only after seeing and responding to the N + 1-trial stimulus. Theory suggests that lagged reinforcement will eliminate a dominant form of implicit discrimination learning. Yet monkeys still learned successfully. Thus, monkeys may have alternative learning algorithms usable when reinforcement is displaced and reinforcement learning undermined. This learning may, as in humans, take a more explicit form. This and related methods that disable associative learning-fostering a possible transition to explicit cognition-could have empirical utility and theoretical significance within comparative psychology. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Cognitive Architecture of Uncertainty.

The authors consider theory in the animal-metacognition literature. Theoretical interpretation was long dominated by associative descriptions, as illustrated in the 2009 special issue. We suggest that this approach risks a self-limiting understanding of animal mind, and an imprecise understanding of the cognitive requirements inherent in metacognition tasks. In fact, some tasks self-entail the need for higher-level decision-making processes, processes that-in humans-we would call explicit, declarative, and conscious. These points are illustrated using the inaugural study on dolphin metacognition. We urge researchers to turn more toward illuminating the cognitive architecture of capacities like metacognition, including illuminating the depth, and structure, the learning/memory systems, the cognitive levels, and the declarative awareness possibly present in animals' minds. The empirical development of this literature demonstrates that researchers are now prepared to do so. This study can produce strong synergies across the allied fields of biopsychology, comparative and cognitive psychology, and neuroscience.

Simultaneous versus prospective/retrospective uncertainty monitoring: The effect of response competition across cognitive levels.

Early animal-metacognition researchers singled out simultaneous metacognition paradigms for theoretical criticism, because these paradigms presented concretely rewarded perceptual responses and the metacognitive response simultaneously. This method potentially introduced associative cues into the situation that could confound the interpretation of the metacognitive response. Evaluating this possibility, we compared humans' metacognitive performances in simultaneous and nonsimultaneous (prospective, retrospective) paradigms that were otherwise identical. Results show that the metacognition response in these tasks is not prompted by associative cues arising from the simultaneous task format. To the contrary, the metacognitive response is used more robustly and accurately when it is removed from direct competition with the primary perceptual responses. Thus, early researchers were correct to judge that the nonsimultaneous paradigms tap metacognition more robustly and sensitively. However, this is probably true because the simultaneous paradigm mingles responses adjudicated on two different cognitive-processing levels. And, in that case, the metacognitive response can be outcompeted and suppressed by the salient presence of primary, concretely rewarded perceptual responses. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Validated methods to identify patients with asthma-COPD overlap in healthcare databases: a systematic review protocol.

INTRODUCTION: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is characterised by patients presenting symptoms of both asthma and COPD. Many efforts have been made to validate different methods of identifying asthma-COPD overlap cases based on symptoms, spirometry and medical history in epidemiological studies using healthcare databases. There are various coding algorithm strategies that can be used and selection depends on targeted validation. The primary objectives of this systematic review are to identify validated methods (or algorithms) that identify patients with ACO from healthcare databases and summarise the reported validity measures of these methods. METHODS: MEDLINE, EMBASE databases and the Web of Science will be systematically searched by using appropriate search strategies that are able to identify studies containing validated codes and algorithms for the diagnosis of ACO in healthcare databases published, in English, before October 2018. For each selected study, we require the presence of at least one test measure (eg, sensitivity, specificity etc). We will also include studies, in which the validated algorithm is compared with an external reference standard such as questionnaires completed by patients or physicians, medical charts review, manual review or an independent second database. For all selected studies, a uniform table will be created to summarise the following vital information: name of author, publication year, country, data source, population, clinical outcome, algorithms, reference standard method of validation and characteristics of the test measure used to determine validity. PROSPERO REGISTRATION NUMBER: CRD42018087472.