Temporal binding and internal clocks

Temporal binding refers to the perceptual attraction of causally related events, which are perceived as closer together in time than unrelated events. This effect is not only characterised by the perceived attraction of cause and effect, but also by a contraction of the interval separating the events. Since the original article on temporal binding (Haggard, Clarke, & Kalogeras, 2002), research has identified the conditions necessary for the effect to occur. While predictability and contiguity are both necessary, it is causality and not intentional action that is the root of the effect (Buehner, 2012). Despite this fruitful work, little is known about how temporal binding is realised. Event perception approaches suggest that binding arises as a realignment of sensory streams. Time perception approaches, in contrast, suggest that binding arises due to a changes in temporal perception during the interval. Given the precedence for the latter approach in the literature (Humphreys & Buehner, 2009; Wenke & Haggard, 2009), I therefore applied an internal clock model of time perception to temporal binding. In Experiments 1 – 4 (Chapter 3), I explored whether binding is effected by the general slowing of a rate of an internal clock. Participants made verbal estimates of either an interval (in causal and noncausal conditions), or of an unrelated event embedded either before or during the interval. I hypothesised that changes in a general clock rate would both affect intervals and embedded events, such that events embedded during causal intervals would be judged as shorter than those embedded during noncausal intervals. The results revealed that causal trial intervals were judged as shorter than noncausal intervals, while no effect was found for embedded events. These results suggested that binding is effected by clock processes specific to cause-effect intervals. Experiments 5 - 8 (Chapter 4) examined whether binding might arise either due to changes 1 in a specific clock rate or to differential timing latencies. Using a temporal discrimination procedure, participants judged whether a variable duration interval was shorter or longer than a reference interval. The point of subjective equality (PSE) was computed for each reference duration, and then modelled using regression. The results revealed a significant binding effect, but more importantly, significant differences in regression slopes between causal and noncausal conditions in three out of four experiments. These results supported the hypothesis of a slower clock rate in temporal binding. In Experiments 9 - 10 (Chapter 5) I verified the results of Chapter 4 by examining discrimination thresholds between two causal and two noncausal intervals. In both experiments (Chapter 5), higher just-noticeable- difference (JND) thresholds were found in causal conditions, supporting the notion of a slower clock rate in cause-effect intervals. Taken together, the present body of work supports the notion that temporal binding is effected by a slower internal clock rate. Future experiments might investigate whether clock slowing in binding is driven by causality or predictability

Temporal binding and internal clocks: No evidence for general pacemaker slowing.

The perception of time is distorted by many factors (e.g., arousal, temperature, age etc.), but is it possible that causality would affect our perception of time? We investigate timing changes in the temporal binding effect, which refers to a subjective shortening of the interval between actions and their outcomes. Four experiments investigated whether binding may be due to variations in the rate of an internal clock. Specifically, we asked whether binding reflects changes to a general timing system, or a dedicated clock unique to causal sequences. We developed a novel experimental paradigm (embedded interval estimation procedure) in which participants made temporal judgments of either causal or non causal intervals, or the duration of an event embedded within that interval. Stimuli and modality were combined factorially, with interval markers and embedded events being either visual or auditory. While we replicated the temporal binding effect, we found no evidence for commensurate changes to time perception of the embedded event, which suggests that temporal binding is effected by changes to a specific and dedicated, rather than a general clock system

The role of time perception in temporal binding: Impaired temporal resolution in causal sequences

Causality affects our perception of time; events that appear as causally related are perceived as closer together in time than unrelated events. This effect is known as temporal binding. One potential explanation of this effect is that causality slows an “internal clock” that is used in interval estimation. To explore this hypothesis, we first examined participants’ perceived duration of a range of intervals between a causal action and an effect, or between two unrelated events. If (apparent) causality slows the internal clock, then plotting perceived duration against actual duration should reveal a shallower slope in the causality condition (a relative compression of perceived time). This pattern was found. We then examined an interesting corollary: that a slower rate during causal sequences would result in reduced temporal acuity. This is what we found: Duration discrimination thresholds were higher for causal compared to non-causal sequences. These results are compatible with a clock-slowing account of temporal binding. Implications for sensory recalibration accounts of binding are discussed

Tropical rainfall predictions from multiple seasonal forecast systems

We quantify seasonal prediction skill of tropical winter rainfall in 14 climate forecast systems. High levels of seasonal prediction skill exist for year‐to‐year rainfall variability in all tropical ocean basins. The tropical East Pacific is the most skilful region, with very high correlation scores, and the tropical West Pacific is also highly skilful. Predictions of tropical Atlantic and Indian Ocean rainfall show lower but statistically significant scores. We compare prediction skill (measured against observed variability) with model predictability (using single forecasts as surrogate observations). Model predictability matches prediction skill in some regions but it is generally greater, especially over the Indian Ocean. We also find significant inter‐basin connections in both observed and predicted rainfall. Teleconnections between basins due to El Niño–Southern Oscillation (ENSO) appear to be reproduced in multi‐model predictions and are responsible for much of the prediction skill. They also explain the relative magnitude of inter‐annual variability, the relative magnitude of predictable rainfall signals and the ranking of prediction skill across different basins. These seasonal tropical rainfall predictions exhibit a severe wet bias, often in excess of 20% of mean rainfall. However, we find little direct relationship between bias and prediction skill. Our results suggest that future prediction systems would be best improved through better model representation of inter‐basin rainfall connections as these are strongly related to prediction skill, particularly in the Indian and West Pacific regions. Finally, we show that predictions of tropical rainfall alone can generate highly skilful forecasts of the main modes of extratropical circulation via linear relationships that might provide a useful tool to interpret real‐time forecasts

Therapeutic options for mucinous ovarian carcinoma

OBJECTIVE: Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guidelines specifically for the systemic management of recurrent MOC. We analyzed data from a large cohort of women with MOC to evaluate the potential for clinical utility from a range of systemic agents. METHODS: We analyzed gene copy number (n = 191) and DNA sequencing data (n = 184) from primary MOC to evaluate signatures of mismatch repair deficiency and homologous recombination deficiency, and other genetic events. Immunohistochemistry data were collated for ER, CK7, CK20, CDX2, HER2, PAX8 and p16 (n = 117-166). RESULTS: Molecular aberrations noted in MOC that suggest a match with current targeted therapies include amplification of ERBB2 (26.7%) and BRAF mutation (9%). Observed genetic events that suggest potential efficacy for agents currently in clinical trials include: KRAS/NRAS mutations (66%), TP53 missense mutation (49%), RNF43 mutation (11%), ARID1A mutation (10%), and PIK3CA/PTEN mutation (9%). Therapies exploiting homologous recombination deficiency (HRD) may not be effective in MOC, as only 1/191 had a high HRD score. Mismatch repair deficiency was similarly rare (1/184). CONCLUSIONS: Although genetically diverse, MOC has several potential therapeutic targets. Importantly, the lack of response to platinum-based therapy observed clinically corresponds to the lack of a genomic signature associated with HRD, and MOC are thus also unlikely to respond to PARP inhibition

The Molecular Origin and Taxonomy of Mucinous Ovarian Carcinoma

Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin. Here we show that MOC is distinct from tumors from other sites and supports a progressive model of evolution from borderline precursors to high-grade invasive MOC. Key drivers of progression identified are TP53 mutation and copy number aberrations, including a notable amplicon on 9p13. High copy number aberration burden is associated with worse prognosis in MOC. Our data conclusively demonstrate that MOC arise from benign and borderline precursors at the ovary and are not extra-ovarian metastases

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

A shared resource for syntactic processing in music and language: Evidence from musicians/non-musicians using local cue manipulation

Patel’s (2003) Shared Syntactic Integration Resource Hypothesis (SSIRH) claims that music and language are represented separately yet are processed according shared networks. According to the model, music and language place syntactic demands on this limited processing resource. The current study aims to test this hypothesis by combining linguistic ambiguity (sentences based on minimal attachment theory) and musical ambiguity (presentation of a non-diatonic chord sequence). The study extends previous research by manipulating local processing cues and examining musician/non-musician differences. A self-paced paradigm is used to present linguistic and musical stimuli, with on-line and off-line measures taken (response times and question accuracies, respectively). Main findings reveal longer processing times for ambiguous stimuli; a significant yet contrary result for condition (faster response times for concurrent music/language tasks); and a partial effect for local musical cue manipulation. The findings suggest a new direction for research into the SSIRH and possible applied benefits