Impact of the Marker Set Configuration on the Accuracy of Gait Event Detection in Healthy and Pathological Subjects

For interpreting outcomes of clinical gait analysis, an accurate estimation of gait events, such as initial contact (IC) and toe-off (TO), is essential. Numerous algorithms to automatically identify timing of gait events have been developed based on various marker set configurations as input. However, a systematic overview of the effect of the marker selection on the accuracy of estimating gait event timing is lacking. Therefore, we aim to evaluate (1) if the marker selection influences the accuracy of kinematic algorithms for estimating gait event timings and (2) what the best marker location is to ensure the highest event timing accuracy across various gait patterns. 104 individuals with cerebral palsy (16.0 ± 8.6 years) and 31 typically developing controls (age 20.6 ± 7.8) performed clinical gait analysis, and were divided into two out of eight groups based on the orientation of their foot, in sagittal and frontal plane at mid-stance. 3D marker trajectories of 11 foot/ankle markers were used to estimate the gait event timings (IC, TO) using five commonly used kinematic algorithms. Heatmaps, for IC and TO timing per group were created showing the median detection error, compared to detection using vertical ground reaction forces, for each marker. Our findings indicate that median detection errors can be kept within 7 ms for IC and 13 ms for TO when optimizing the choice of marker and detection algorithm toward foot orientation in midstance. Our results highlight that the use of markers located on the midfoot is robust for detecting gait events across different gait patterns.

Reconstructing transcriptional histories by CRISPR acquisition of retron-based genetic barcodes

Biological processes depend on the differential expression of genes over time, but methods to make true physical recordings of these processes are limited. Here we report a strategy for making time-ordered recordings of transcriptional events into living genomes. We do this via engineered RNA barcodes, based on prokaryotic retrons, which are reverse-transcribed into DNA and integrated into the genome using the CRISPR-Cas system. This approach enables the targeted recording of time-ordered transcriptional events in cells. The unidirectional integration of barcodes by CRISPR integrases enables reconstruction of transcriptional event timing based on a physical record via simple, logical rules rather than relying on pre-trained classifiers or post-hoc inferential methods.

Derivation of visual timing-tuned neural responses from early visual stimulus representations

Quantifying the timing (duration and frequency) of brief visual events is vital to human perception, multisensory integration and action planning. Tuned neural responses to visual event timing have been found in areas of the association cortices implicated in these processes. Here we ask whether and where the human brain derives these timing-tuned responses from the responses of early visual cortex, which monotonically increase with event duration and frequency. Using 7T fMRI and neural model-based analyses, we find a gradual transition from monotonically increasing to timing-tuned neural responses beginning in area MT/V5. Therefore, successive stages of visual processing gradually derive timing-tuned response components from the inherent modulation of sensory responses by event timing. This additional timing-tuned response component was independent of retinotopic location. We propose that this hierarchical derivation of timing-tuned responses from sensory processing areas quantifies sensory event timing while abstracting temporal representations from the spatial properties of their inputs.

Expectancy-based rhythmic entrainment as continuous Bayesian inference

When presented with complex rhythmic auditory stimuli, humans are able to track underlying temporal structure (e.g., a “beat”), both covertly and with their movements. This capacity goes far beyond that of a simple entrained oscillator, drawing on contextual and enculturated timing expectations and adjusting rapidly to perturbations in event timing, phase, and tempo. Previous modeling work has described how entrainment to rhythms may be shaped by event timing expectations, but sheds little light on any underlying computational principles that could unify the phenomenon of expectation-based entrainment with other brain processes. Inspired by the predictive processing framework, we propose that the problem of rhythm tracking is naturally characterized as a problem of continuously estimating an underlying phase and tempo based on precise event times and their correspondence to timing expectations. We present two inference problems formalizing this insight: PIPPET (Phase Inference from Point Process Event Timing) and PATIPPET (Phase and Tempo Inference). Variational solutions to these inference problems resemble previous “Dynamic Attending” models of perceptual entrainment, but introduce new terms representing the dynamics of uncertainty and the influence of expectations in the absence of sensory events. These terms allow us to model multiple characteristics of covert and motor human rhythm tracking not addressed by other models, including sensitivity of error corrections to inter-event interval and perceived tempo changes induced by event omissions. We show that positing these novel influences in human entrainment yields a range of testable behavioral predictions. Guided by recent neurophysiological observations, we attempt to align the phase inference framework with a specific brain implementation. We also explore the potential of this normative framework to guide the interpretation of experimental data and serve as building blocks for even richer predictive processing and active inference models of timing.

Temporal Regularity May Not Improve Memory for Item-Specific Detail

Regularities in event timing allow for the allocation of attention to critical time-points when an event is most likely to occur, leading to improved visual perception. Results from recent studies indicate that similar benefits may extend to memory for scenes and objects. Here, we investigated whether benefits of temporal regularity are evident when detailed, item-specific representations are necessary for successful recognition memory performance. In Experiments 1 and 2, pictures of objects were presented with either predictable or randomized event timing, in separate encoding blocks. In the test phase, old and new objects were presented, intermixed with perceptually similar exemplars of encoded objects. In Experiment 3 we attempted to replicate previously reported memory enhancements for scenes. In contrast to predictions, temporal regularity did not affect response times (RT) or improve recognition memory accuracy in any of our experiments. These results suggest that any effects of temporal expectation on memory are subtle and may be sensitive to minor changes in task parameters. In sum, indirect upregulation of attention through imposed temporal structure may not be sufficient to have downstream effects on memory performance.

Cortical Microcircuitry of Executive Control and Source of Associated Event-Related Potentials

Medial frontal cortex enables executive control by signaling conflict, monitoring and predicting events and outcomes, and goal maintenance, indexed by event-related potentials (ERP). In monkeys performing a saccade countermanding (stop-signal) task, we recorded EEG over and neural spiking across all layers of the supplementary eye field (SEF). Neurons did not contribute to reactive response inhibition. Those signaling response conflict and tracking and predicting the timing of events for successful stopping had different spike widths and were concentrated differently across layers. Conflict neurons were in all layers and those encoding temporal parameters were concentrated in L2/3 and L5. The N2 indexed reward association with variation of polarization predicted by conflict and event timing neurons in L2/3 but not L5/6. The P3 indexed the timing of the upcoming event with variation of polarization predicted by event timing neurons in L2/3 but not L5/6. These findings reveal novel features of the cortical microcircuitry supporting executive control and producing associated ERP.