Temporal Order Research Articles

Habituation disorders in auditory middle latency response of persistent postural-perceptual dizziness patients.

To study habituation disorders in auditory middle latency response (AMLR) to repetitive stimuli of persistent postural-perceptual dizziness (PPPD) patients. Twenty-eight PPPD (10 men and 18 women, mean 59.5 years of age, 26-81 years of age) were enrolled. For comparison, data of 13 definite vestibular migraine (VM) patients (3 men, 10 women, mean age 45.5), 13 definite unilateral Meniere's disease (MD) patients (2 men, 11 women, mean age 50.6), and 8 healthy control (HC) subjects (2 men, 6 women, mean age 37.1) in the previous study were utilized. The electrodes were placed on the vertex and the spinal process of the fifth cervical vertebra. Clicks (0.1 msec, 70 dB nHL) were binaurally presented and averaged (800 times). Averaged responses were divided into 4 sets (S1 to S4) according to the temporal order. As peaks, Na, and Pa were identified, and relative Na-Pa amplitudes in S2-S4 to S1 were analyzed. The mean relative amplitude of PPPD patients showed lack of habituation (potentiation) as shown in VM patients, although the extent of potentiation was weaker than VM. Comparison of relative S4 amplitudes showed significant differences among the 4 groups (p = 0.0013 one-way ANOVA), Multiple comparison revealed significant differences between PPPD and MD (p = 0.0337 Dunnet's test). PPPD patients showed lack of habituation (potentiation) of Na-Pa amplitude in AMLR to repetitive stimuli. Lack of habituation (potentiation) might be associated with sensory processing disorders in PPPD.

Postpartum Maternal Anxiety Affects the Development of Food Allergy Through Dietary and Gut Microbial Diversity During Early Infancy.

We aimed to investigate the mediating factors between maternal anxiety and the development of food allergy (FA) in children until 2 years from birth. In this longitudinal cohort of 122 mother-child dyads from pregnancy to 24 months of age, we regularly surveyed maternal psychological states, infant feeding data, and allergic symptoms and collected stool samples at 6 months of age for microbiome analysis. Considering the temporal order of data collection, we investigated serial mediating effects and indirect effects among maternal anxiety, dietary diversity (DD), gut microbial diversity, and FA using structural equation modeling. Among the 122 infants, 15 (12.3%) were diagnosed with FA. Increased maternal anxiety between 3 and 6 months after delivery was associated with a lower DD score. Infants with low DD at 4 months showed low gut microbial richness, which was associated with FA development. When the infants were grouped into 4 subtypes, using consensus clustering of 13 gut bacteria significantly associated with maternal anxiety and DD, Prevotella, Eubacterium, Clostridiales and Lachnospiraceae were more abundant in the group with lower FA occurrence. Postpartum maternal anxiety, mediated by reduced DD and gut microbial diversity, may be a risk factor for the development of FA in infants during the first 2 years of life.

Ontological (In)Security - Art Students’ Experience of Agency in the Educational Reality During the Pandemic

Objectives of the study: The purpose of the study is to reconstruct the experiences of art students during the Covid-19 pandemic. The research question is as follows: What image of the everyday life of remote education emerges from the reconstruction of the experiences of students who were previously assigned to extreme groups in terms of their perceived proficiency?
 Research methods: Due to the different objectives’ for specific questions – involving nomothetic explanation in some areas (basic descriptive statistics, comparison of selected subfields, logistic regression) and idiographic explanation in others (qualitative content analysis) – the research used a quantitative and qualitative strategy.
 Brief description of the context of the issue: Art schools provide unique educational opportunities as teachers-artists have a personal influence on students through face-to-face interaction. The pandemic has presented these schools with an unprecedented challenge, on a scale that had not been seen before. In the research presented here, voice was given to the students, who were considered experts in their own cause. Their experiences, as a multidimensional construct, were located theoretically in the context of the threefold framework of temporal order, space and relationship, and Bruner’s concept of the role of support in child development.
 Research findings: The results show a link between perceived levels of ontological security and the way students functioned at school during the pandemic. Psychological well-being was affected more strongly in those with a low sense of agency, who often balanced on the verge of ontological security and experienced reality in a traumatic way, while students with a high sense of agency tended to focus on the benefits rather than losses.
 Conclusions and/or recommendations: Locating students on the continuum of a sense of agency brought a fresh perspective on the different ways in which young artists with and without a disturbed sense of ontological security experienced school during the pandemic. Important recommendations include continuing multidirectional support measures of a pedagogical and psychological nature undertaken by many institutions, which should be aimed at art students, their parents and teachers.

Building a business process model using temporal knowledge when implementing process management

The article’s subject matter are business processes, which are a sequence of work, which are provided with resources and create products and services that are valuable for the customers of such processes. The aim is to develop an approach to solving the problems of implementing process management based on the automated detection of temporal knowledge, which makes it possible to establish conditions and restrictions on the execution of process actions, considering their actual temporal order, and thus makes it possible to consider the personal knowledge of process performers both in building and refining their model. Objectives: To structure the process management tasks, considering the interaction between the subtasks of process management implementation and business process management tasks; to develop a method for building a business process prototype using temporal knowledge. The approaches used are process management methods, process mining methods, temporal knowledge methods. The scientific novelty of the obtained results is as follows. The article develops a method for building a model of the business process "as it is", performed in an enterprise, using temporal knowledge. The method includes stages of forming temporal knowledge in the form of rules that determine the sequence of process actions in time, selection of subsets of rules that specify sequential and parallel or alternative execution of process actions, and stages of building the business process model in the form of a workflow graph that considers the identified temporal rules. In practice, the method creates conditions for the implementation of continuous improvement of the business process based on the iterative identification and further use of the tacit knowledge of the performers, which is reflected in the temporal rules.

ЈОШ О ТЕМПОРАЛНИМ ПРЕДЛОШКО-ПАДЕЖНИМ ФОРМАМА У ГОВОРУ БАНАТСКЕ ЦРНЕ ГОРЕ

This paper deals with the case formalisers of the indirect temporal identification – meaning of successive, on the corpora of the vernacular of Banat Montenegro. Otherwise, this article is connected with earlier research concerning of temporal determinative system case within the simultaneity semantic subfield in the mentioned vernacular (Simić 2017). Now we analyze prepositional-case constructions with the meaning of succession, specified as anteriority or posteriority aspects within temporal order. Also, this article deals with the forms with the meaning of unspecified succession. Consequently, the analyze of the system of prepositional-case constructions with the meaning of temporal identification in the vernacular of Banat Montenegro will be completed. A detailed analysis of all registered prepositional-case forms with the semantic feature of succession will discover the degree of the basic features which are characteristic for the majority of Shtokavian speeches and contemporary Serbian, also. This applies to the terms of the choice of case form and in terms of the inventory of prepositional units, primarily. Considering peripheral position of the vernacular of Banat Montenegro on the Serbian dialect map, as well as cross-linguistic interference, its structural distinction is expected. Therefore, we assume that the archaic features have been preserved, on the one hand. But, on the other hand, different innovation processes are expected, primarily within the analytisation of the case system, but also in the copying of Romanian models, etc.

PORÓWNANIE TESTÓW SEKWENCJI CZĘSTOTLIWOŚCI OPARTYCH NA SAMOGŁOSKACH I TONACH

IntroductionThe pitch pattern test (PPT) is a test of temporal ordering in which a subject needs to correctly repeat a sequence of three auditory stimuli comprised of high and low frequencies. Traditionally, tones are used, but here the aim was to develop a PPT using vowels. The tests were done in young adults and a comparison was made between the two methods.Material and methodsThe study involved 40 young adults with normal hearing sensitivity and was done in two phases. Phase I involved the development of a PPT using the vowel /a/, and in Phase II the test was administered. A comparison was made with the PPT based on tones. In both tests, stimuli were delivered monaurally.ResultsAll participants were able to do the PPT using either vowels or tones. No ear or gender effects were observed. However, the mean scores for PPT using tones were notably better than those obtained using vowels.ConclusionsThe present study has developed a PPT using the vowel /a/ and has compared scores with the tonal pitch pattern test. The absence of a ceiling effect in the PPT using a vowel gives it an advantage in terms of potential clinical utility. The strong positive correlation between the PPT using a vowel and the PPT using a tone shows a significant relationship between the two tests in the specific domain of temporal ordering.

Static and dynamic fMRI-derived functional connectomes represent largely similar information.

Functional connectivity (FC) of blood oxygen level-dependent (BOLD) fMRI time series can be estimated using methods that differ in sensitivity to the temporal order of time points (static vs. dynamic) and the number of regions considered in estimating a single edge (bivariate vs. multivariate). Previous research suggests that dynamic FC explains variability in FC fluctuations and behavior beyond static FC. Our aim was to systematically compare methods on both dimensions. We compared five FC methods: Pearson's/full correlation (static, bivariate), lagged correlation (dynamic, bivariate), partial correlation (static, multivariate), and multivariate AR model with and without self-connections (dynamic, multivariate). We compared these methods by (i) assessing similarities between FC matrices, (ii) by comparing node centrality measures, and (iii) by comparing the patterns of brain-behavior associations. Although FC estimates did not differ as a function of sensitivity to temporal order, we observed differences between the multivariate and bivariate FC methods. The dynamic FC estimates were highly correlated with the static FC estimates, especially when comparing group-level FC matrices. Similarly, there were high correlations between the patterns of brain-behavior associations obtained using the dynamic and static FC methods. We conclude that the dynamic FC estimates represent information largely similar to that of the static FC.

A graph neural network with context filtering and feature correction for conversational emotion recognition

Conversational emotion recognition represents an important machine-learning problem with a wide variety of deployment possibilities. The key challenge in this area is how to properly capture the key conversational aspects that facilitate reliable emotion recognition, including utterance semantics, temporal order, informative contextual cues, speaker interactions as well as other relevant factors. In this paper, we present a novel Graph Neural Network approach for conversational emotion recognition at the utterance level. Our method addresses the outlined challenges and represents conversations in the form of graph structures that naturally encode temporal order, speaker dependencies, and even long-distance context. To efficiently capture the semantic content of the conversations, we leverage the zero-shot feature-extraction capabilities of pre-trained large-scale language models and then integrate two key contributions into the graph neural network to ensure competitive recognition results. The first is a novel context filter that establishes meaningful utterance dependencies for the graph construction procedure and removes low-relevance and uninformative utterances from being used as a source of contextual information for the recognition task. The second contribution is a feature-correction procedure that adjusts the information content in the generated feature representations through a gating mechanism to improve their discriminative power and reduce emotion-prediction errors. We conduct extensive experiments on four commonly used conversational datasets, i.e., IEMOCAP, MELD, Dailydialog, and EmoryNLP, to demonstrate the capabilities of the developed graph neural network with context filtering and error-correction capabilities. The results of the experiments point to highly promising performance, especially when compared to state-of-the-art competitors from the literature.

Strategie narracyjne destabilizujące porządek czasowy w neoserialach

The serial narrative mode, regularly used in episodic productions with a repetitive plot structure, is now rarely used. As for contemporary series, researchers agree that filmmakers adhere to a new paradigm of television storytelling which Jason Mittell termed “narrative complexity.” One of its distinguishing features are temporal disturbances in which the creators use various narrative strategies that destabilize the temporal order, ranging from flashbacks that fill in the plot gaps to “mind game” strategies. In this article I analyze narrative strategies disrupting the linear plot in quality TV dramas and the characteristics of formal procedures used by artists.

Emergence of replication timing during early mammalian development.

DNA replication enables genetic inheritance across the kingdoms of life. Replication occurs with a defined temporal order known as the replication timing (RT) programme, leading to organization of the genome into early- or late-replicating regions. RT is cell-type specific, is tightly linked to the three-dimensional nuclear organization of the genome1,2 and is considered an epigenetic fingerprint3. In spite of its importance in maintaining the epigenome4, the developmental regulation of RT in mammals in vivo has not been explored. Here, using single-cell Repli-seq5, we generated genome-wide RT maps of mouse embryos from the zygote to the blastocyst stage. Our data show that RT is initially not well defined but becomes defined progressively from the 4-cell stage, coinciding with strengthening of the A and B compartments. We show that transcription contributes to the precision of the RT programme and that the difference in RT between the A and B compartments depends on RNA polymerase II at zygotic genome activation. Our data indicate that the establishment of nuclear organization precedes the acquisition of defined RT features and primes the partitioning of the genome into early- and late-replicating domains. Our work sheds light on the establishment of the epigenome at the beginning of mammalian development and reveals the organizing principles of genome organization.

Physical activity and specific symptoms of depression: A pooled analysis of six cohort studies

BackgroundThe association between physical activity (PA) and depression is well-established, but the details that explain this association remain elusive. We examined whether PA is differentially associated with specific symptoms of depression (e.g., cognitive vs somatic symptoms), and whether these associations follow a dose-response pattern with respect to intensity or frequency of PA. MethodsCross-sectional analyses were based on 6 samples of the continuous U.S. National Health and Nutrition Examination Surveys (NHANES) carried out between 2007 and 2018 (n = 28,520). Depressive symptoms were assessed with Patient Health Questionnaire 9 (PHQ-9). Information about PA (vigorous, moderate, and daily commuting by foot or bike) and covariates was self-reported. ResultsAfter adjusting for education, health behaviors, body-mass index, physical functioning, and all the other depressive symptoms, lower PA was specifically associated with four depressive symptoms: loss of interest/pleasure, feeling down/hopeless, fatigue, and changes in appetite (odds ratios from 0.94 to 0.59). A monotonic dose-response pattern on PA amount was observed only for interest/pleasure and fatigue, and these associations were independent of PA intensity. LimitationsCross-sectional data did not allow us to assess temporal ordering. Both depressive symptoms and PA were self-reported, which may induce bias. ConclusionLow PA may be linked to depressive symptoms particularly through the symptoms of anhedonia and fatigue. Given that their association with PA amount follows a dose-response pattern and is independent of PA intensity, we hypothesize that behavioral activation and exposure to rewarding experiences might help to explain why PA alleviates depression.

Mémoire, nostalgie et « la fin de l’utopie » à l’âge du « présentisme »

"Less than a decade after the proclamation of “the end of history”, the anxieties about “the end of utopia” are gaining ground in the intellectual field all over the world, in the context of both “the crisis of the future” and the haunting of the present by the painful pasts. The latter two are the main consequences of the fracture in the contemporary temporal order – occurred in the ‘70s and deepened after the fall of the Iron Curtain – which defines the “presentist regime of historicity”. These dynamics are counterbalanced, in the same period, by a “global epidemic of nostalgia”, including the commodified forms of “retromania”, that reveals the presentist “faces of utopianism”, from the non-instrumental “retrospective utopias” – as poles of “existential” types of reflective nostalgic practices – to the instrumental “retrotopias” based on the “restorative nostalgia”, which were mobillized in the contemporary memory wars, starting from the ‘80s. Reflecting the tensions between the fixation on the traumatic legacy of the “age of extremes” and the apprehensions about “the future of nostalgia”, the presentist dynamics of multidirectional memory discloses conflictual landscapes (social, cultural, and political), from the mnemonic turn of the ’70s and the ‘80s – which has arisen against the background of the decline of both welfare state and the nation-states, and of the global economic crisis – to the post–Cold War contests around “the divised memories” of “Europe’s Europes”, coexisting with the clashes of contradictory “faces” of nostalgia and utopia. Keywords: presentism, multidirectional memory, nostalgia, retrospective utopia, retrotopia"

Longitudinal associations between lie evaluations and frequency: The moderating role of age.

While previous studies have demonstrated correlations between children and adolescents' evaluations of lies and lie-telling behaviors, the temporal order of these associations over time and changes across this developmental period remain unexamined. The current study examined longitudinal associations among children and adolescents' (N=1128; Mage=11.54, SD=1.68, 49.80% male, and 83.6% white) evaluations of lies to parents for autonomy and lie-telling frequency to parents and friends. Autoregressive cross-lagged analysis revealed longitudinal associations moderated by age. Among children, evaluations of lies predicted greater lie-telling rates over time. Conversely, among adolescents, lie-telling frequency predicted lie evaluations over time, and evaluations predicted lying to parents over time. These results demonstrate a novel developmental pattern of the associations between moral evaluations of lies and lie-telling. RESEARCH HIGHLIGHTS: Children and adolescents' evaluations of lie-telling and lie-telling frequency were associated longitudinally, but the direction of this association was moderated by age. Among children, more positive lie evaluations predicted greater lie-telling to parents and friends over time. Among adolescents, more positive lie evaluations predicted lying more often to parents over time; lying more to parents and friends predicted more positive evaluations over time. These findings suggest a novel developmental pattern regarding the temporal order of the association between evaluations of lie-telling and lie-telling frequency.

Episodic memory during middle childhood: What is developing?

Whereas previous research has concentrated on the emergence of episodic memory during the early years, fewer investigations have explored the details of this development through middle and late childhood. Considerable variation in task demands and testing methodologies have rendered the trajectory of episodic memory during this period unclear, particularly with regard to which elements are in a state of change at which time. This study separately assessed memory for item, location, and temporal order, as well as integrated what–where–when (WWW) information using a WWW memory test (the Treasure Hunt task), with 84 children aged 6 to 12 years. Two versions of the task were used, varying in the degree of retrieval support while keeping encoding constant. Results show that episodic memory continued to develop across this period, with individual item, spatial, temporal, and WWW memory all improving relatively linearly with age. These improvements were underpinned by both the associative binding and strategic control processes. These findings suggest that it is not any one element of episodic memory that is driving development during this period but that all aspects are continuing to mature in parallel.

A comparison of Rosenbrock–Wanner and Crank–Nicolson time integrators for atmospheric modelling

AbstractNonhydrostatic atmospheric models often use semi‐implicit temporal discretisations in order to negate the time‐step limitation of explicitly resolving the fast acoustic and gravity waves. Solving the resulting system to machine precision using Newton's method is considered prohibitively expensive, and so the nonlinear solver is typically truncated to a fixed number of iterations, often using an approximate Jacobian matrix that is reassembled only once per time step. The present article studies the impact of using various third‐order, four stage Rosenbrock–Wanner schemes, where integration weights are chosen to meet specific stability and order conditions, in comparison to a Crank–Nicolson time discretisation, as is done in the UK Met Office's LFRic model. Rosenbrock–Wanner schemes present a promising alternative on account of their ability to preserve their temporal order with only an approximate Jacobian, and may be constructed to be stiffly‐stable, so as to ensure the decay of fast unresolved modes. These schemes are compared for the 2D rotating shallow‐water equations and the 3D compressible Euler equations at both planetary and nonhydrostatic scales and are shown to exhibit improved results in terms of their energetic profiles and stability. Results in terms of computational performance are mixed, with the Crank–Nicolson method allowing for longer time steps and faster time to solution for the baroclinic instability test case at planetary scales, and the Rosenbrock–Wanner methods allowing for longer time steps and faster time to solution for a rising bubble test case at nonhydrostatic scales.

Comparison of Focal Hippocampal T2‐Weighted MRI and Whole‐Brain T1‐Weighted MRI for Detection of Longitudinal Atrophy Using Deep Learning‐Based and Conventional Approaches

AbstractBackgroundLongitudinal measurement of medial temporal lobe (MTL) atrophy is shown to be effective in measuring Alzheimer’s disease (AD) progression and has been extensively studied on T1‐weighted MRI. However, there has been little work analyzing atrophy on high‐resolution T2‐weighted MRI of the hippocampal region, and it is unknown which MRI modality would yield a more effective biomarker of disease progression. We compare atrophy measurements derived from T1 and T2‐weighted MRI using a deep learning framework DeepAtrophy and a deformation‐based morphometry method ALOHA.MethodT2‐weighted MRI of 481 participants from ADNI2/3 are included in the study. DeepAtrophy was trained on 74 participants and evaluated on 407. During training, DeepAtrophy explicitly infers temporal information, such as the scan temporal order for a single scan pair and which image pair has a longer scan time interval for multiple scan pairs. During inference, DeepAtrophy predicts a “total progression score” for each scan pair. This score is expected to be higher (more progression) in individuals with more advanced AD. A similar experiment was conducted using T1‐weighted MRI from 481 ADNI2/GO participants (partially overlapping with T2‐weighted experiment). ALOHA pipelines tailored for T1‐weighted and hippocampal T2‐weighted MRI were evaluated on the same subjects and scan pairs as DeepAtrophy.ResultFor both T1 and T2‐weighted MRI, DeepAtrophy is more accurate, compared with ALOHA, in inferring the temporal order of a pair of longitudinal scans. In hypothetical one‐year and two‐years clinical trials scenarios simulated using ADNI data, DeepAtrophy has an improvement over ALOHA in detecting differences in progression between disease groups in both imaging modalities. The strongest effect for differentiating between Amyloid‐positive and Amyloid‐negative cognitively unimpaired group was obtained using DeepAtrophy progression measures on T2‐weighted MRI.ConclusionThis study supports the potential of high‐resolution focal T2‐weighted MRI of the hippocampus as a longitudinal biomarker of early AD progression suitable for future clinical trials.

Multi‐modal Imaging‐based peudotime analysis for AD progression

AbstractBackgroundAlzheimer’s disease (AD) progresses along a continuum and begins many years before symptom onset. AD takes a long progression time, making it hard to study the entire spectrum of AD development. Pseudotime analysis widely used in cell lineage analysis have been applied to AD gene expression data to understand the molecular changes along progression. In this work, we performed a neuroimaging‐based pseudotime analysis to explore the progression patterns of different imaging modalities.MethodData were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (https://adni.loni.usc.edu/). Data from three imaging modalities were collected including MRI (N = 1684), Amyloid (N = 1041), and Tau (N = 540) (Table.1). Out of those, 223 subjects have all three modalities. We tested four different pseudotime analysis tools: PHATE, MONOCLE3, Slingshot, and Destiny. MRI, Amyloid, Tau, and the combined multi‐modality data were used to estimate the pseudotime respectively. Only PHATE returned non‐reversed pseudotime and clear disease trajectoriesResultAmyloid derived pseudotime best captures the continuum of disease progression and differentiate diagnosis groups the best (Fig.1(b,f)). It also showed better correlation with clinical cognition scores than the composite amyloid measure (Fig.2(b,d)). Multi‐modality derived pseudotime reveals turning point of Amyloid and Tau. We found that the accumulation of Amyloid starts to accelerate when the composite SUVR reaches ∼1.2, which agrees well with existing findings (Fig.2(g,h)). Such turning point does not exist for amyloid derived pseudotime. It also reveals temporal order of brain changes within and across modalities (Fig.2(e,f)), where we observed overall amyloid changes starts early (i.e., small pseudotime) and accelerates earlier than overall brain atrophy and Tau deposition. With a closer look into Tau regions, we found Tau deposition in BRAAK 1 regions accumulates in a faster rate than those inBRAAK34 and BRAAK56 regions.ConclusionPseudotime analysis has a great potential for us to better understand the progression of Alzheimer’s disease. New approaches to fully leverage the longitudinal imaging data could provide a refined view of imaging changes and their co‐occurance pattern along AD progression. Longitudinal data in pseudotime analysis could also help capture the subtle changes in very early stage and therefore would likely provide some valuable insights to improve early diagnosis.

Association between basal forebrain and medial temporal lobe tau, and gray matter volume

AbstractBackgroundTau pathology is a hallmark of Alzheimer’s disease (AD). The basal forebrain (BF) is a significant cholinergic projection site with cholinergic groups 1‐3 (Ch1‐3) projecting to the hippocampus, hypothalamus, and olfactory bulb, and group 4 (Ch4) projecting to the cortical mantle and amygdala. Braak stage 1 includes BF tau and recent literature suggests BF degeneration precedes medial temporal lobe (MTL) degeneration, thus implicating early involvement of the BF in AD. This study examines BF 18F‐flortaucipir (FTP) retention and gray matter (GM) volume, and their associations with MTL FTP retention and GM volume.MethodData were acquired for 111 older adults (Table 1) in the Baltimore Longitudinal Study of Aging. Binary masks for BF subregions Ch1‐3 and Ch4 were generated using a probabilistic atlas (Figure 1). We computed mean standardized uptake value ratio (SUVR) using an inferior cerebellar GM reference region and mean GM volume using average voxel‐based morphometry values for each BF subregion. Colocalized relationships between BF tau and volume were assessed using Pearson correlations. Proximal relationships between BF tau/GM and MTL tau/GM were assessed at the voxel level controlling for age, sex, and intracranial volume and corrected for multiple comparisons using non‐parametric permutations.ResultsWithin the BF, FTP‐SUVR in Ch1‐3 was strongly related to FTP‐SUVR in Ch4, and FTP‐SUVR was associated with larger volume in Ch1‐3, but not Ch4 (Figure 2). Voxelwise analyses showed strong BF‐MTL associations with higher Ch1‐3 and Ch4 FTP‐SUVR associated with higher FTP‐SUVR throughout the MTL. The strongest associations were observed anteriorly (amygdala, peri/entorhinal cortices) and medially along the longitudinal axis of the hippocampus/parahippocampal gyrus. Moreover, for both BF Ch groups, larger volume was associated with larger MTL volume. This association was strongest in the amygdala and hippocampal head and body.ConclusionAs expected, BF FTP‐SUVR was positively associated with MTL FTP‐SUVR, and BF volume was positively associated with MTL GM volume, supporting the use of these BF measures. Further analysis is necessary to better understand the positive associations between BF FTP‐SUVR and GM volume and to assess the temporal ordering of FTP‐SUVR accumulation in the BF and MTL.

Discovery of causal relations of risk factors using Mendelian randomisation and genetic colocalization with UK Biobank data

AbstractMany risk factors, disease traits and comorbidities have been associated with Alzheimer Disease (AD). However, given the long subclinical development of the disease it is difficult to establish temporal order or to rule out shared aetiologies in observational research. Novel analytical molecular epidemiology approaches can be used in AD to investigate potential causality. Mendelian randomisation analysis is an approach where genetic instruments are used as a proxy for the exposure and allow us to investigate the causality of the associations in an observational setting. By selecting genetic instruments MR can be extended to proxy a drug target which allows to mimic the effect of medications targeting that particular gene. Colocalization is another method that tests whether a single genetic variant is driving the association of a shared gene for two traits or disorders. The availability of large‐scale data in UK Biobank including genome‐wide association data (GWAS) and whole genome sequencing (WGS) with a range of questionnaire data, physical measurements, proteomics and other biological measurements and clinical phenotypes has the potential to develop new knowledge on AD aetiology using these new approaches. For example, we were able to study the association between features from MRI brain imaging with AD through the MR approach and show associations between genetically predicted brain iron accumulation in different brain areas with AD risk. In another approach, we were able to study pleiotropic genetic variants that affect both cardiovascular traits and AD and through colocalization identify genes that are likely to be causal for both diseases. Using the wealth of phenotypic data in UK Biobank we were able to further explore the effect of these genes across the phenome and exposome. Further molecular data is expected to be released in UK biobank including proteomics and enhance the study of molecular fingerprints of AD and to extrapolate this knowledge to medications that target them and to elucidate underlying disease pathways.

The less complex temporal patterns of resting‑state EEG activity, the lower the visual temporal order threshold.

Speech understanding, watching a movie, listening to music etc., requires perception of the temporal order of at least two incoming events. A history of performing these tasks may be reflected in spontaneous brain activity. Here, we examined the relationship between the complexity (temporal dynamics) of resting‑state EEG (rsEEG) signal, assessed using the multivariate MultiScale Entropy (mMSE) algorithm, and the perception of event ordering, indexed by a visual temporal order threshold (TOT), i.e., the minimum duration necessary to correctly identify the before‑after relation between two stimuli. Healthy adolescents and young adults performed a psychophysical task measuring the TOT and underwent an eyes‑closed rsEEG study. The features of mMSE vectors, namely the area under curve (AUC) that represents total signal complexity, as well as the MaxSlope and the AvgEnt, corresponding to the entropy at fine‑ and coarse‑grained timescales, respectively, were obtained for the central (midline), anterior, middle and posterior channel sets. The greater the AUC and AvgEnt values in the central, left and right posterior areas, and the higher AUC in the right middle region, the higher the TOT. The most significant relationships were found for the midline electrodes (Fz, Cz, Pz, Oz). There were no significant correlations between the MaxSlope values and the TOT. To the best of our knowledge, this is the first study demonstrating that spontaneous EEG signal complexity is associated with the temporal order perception of two stimuli presented in rapid succession. Our findings may indicate that low total and coarse entropy levels of rsEEG signal are beneficial for visual temporal order judgments.