Computation on demand: Action-specific representations of visual task features arise during distinct movement phases.

The intention to act influences the computations of various task-relevant features. However, little is known about the time course of these computations. Furthermore, it is commonly held that these computations are governed by conjunctive neural representations of the features. But, support for this view comes from paradigms arbitrarily combining task features and affordances, thus, requiring representations in working memory. Therefore, the present study used electroencephalography and a well-rehearsed task with features that afford minimal working memory representations to investigate the temporal evolution of feature representations and their potential integration in the brain. Female and male human participants viewed and grasped objects or touched them with a knuckle. Objects had different shapes and were made of heavy or light materials with shape and weight being relevant for grasping, not for "knuckling." Using multivariate analysis showed that representations of object shape were similar for grasping and knuckling. However, only for grasping did early shape representations reactivate at later phases of grasp planning, suggesting that sensorimotor control signals feed back to early visual cortex. Grasp-specific representations of material/weight only arose during grasp execution after object contact during the load phase. A trend for integrated representations of shape and material also became grasp-specific but only briefly during Movement onset. These results suggest that the brain generates action-specific representations of relevant features as required for the different subcomponents of its action computations. Our results argue against the view that goal-directed actions inevitably join all features of a task into a sustained and unified neural representation.Significance statement The idea that all the features of a task are integrated into a joint representation or event file is widely supported but importantly based on paradigms with arbitrary stimulus-response combinations. Our study is the first to investigate grasping using electroencephalography to search for the neural basis of feature integration in such a daily-life task with overlearned stimulus-response mappings. Contrary to the notion of event files we find limited evidence for integrated representations. Instead, we find that task-relevant features form representations at specific phases of the action, suggesting that action intentions reactivate representations of relevant features. Our results show that integrated representations do not occur universally for any kind of goal-directed behaviour but in a manner of computation on demand.

Characterizing the limitations of using diagnosis codes in the context of machine learning for healthcare.

BACKGROUND: Diagnostic codes are commonly used as inputs for clinical prediction models, to create labels for prediction tasks, and to identify cohorts for multicenter network studies. However, the coverage rates of diagnostic codes and their variability across institutions are underexplored. The primary objective was to describe lab- and diagnosis-based labels for 7 selected outcomes at three institutions. Secondary objectives were to describe agreement, sensitivity, and specificity of diagnosis-based labels against lab-based labels. METHODS: This study included three cohorts: SickKids from The Hospital for Sick Children, and StanfordPeds and StanfordAdults from Stanford Medicine. We included seven clinical outcomes with lab-based definitions: acute kidney injury, hyperkalemia, hypoglycemia, hyponatremia, anemia, neutropenia and thrombocytopenia. For each outcome, we created four lab-based labels (abnormal, mild, moderate and severe) based on test result and one diagnosis-based label. Proportion of admissions with a positive label were presented for each outcome stratified by cohort. Using lab-based labels as the gold standard, agreement using Cohen's Kappa, sensitivity and specificity were calculated for each lab-based severity level. RESULTS: The number of admissions included were: SickKids (n = 59,298), StanfordPeds (n = 24,639) and StanfordAdults (n = 159,985). The proportion of admissions with a positive diagnosis-based label was significantly higher for StanfordPeds compared to SickKids across all outcomes, with odds ratio (99.9% confidence interval) for abnormal diagnosis-based label ranging from 2.2 (1.7-2.7) for neutropenia to 18.4 (10.1-33.4) for hyperkalemia. Lab-based labels were more similar by institution. When using lab-based labels as the gold standard, Cohen's Kappa and sensitivity were lower at SickKids for all severity levels compared to StanfordPeds. CONCLUSIONS: Across multiple outcomes, diagnosis codes were consistently different between the two pediatric institutions. This difference was not explained by differences in test results. These results may have implications for machine learning model development and deployment.

Development and validation of the SickKids Enterprise-wide Data in Azure Repository (SEDAR).

Objectives: To describe the processes developed by The Hospital for Sick Children (SickKids) to enable utilization of electronic health record (EHR) data by creating sequentially transformed schemas for use across multiple user types. Methods: We used Microsoft Azure as the cloud service provider and named this effort the SickKids Enterprise-wide Data in Azure Repository (SEDAR). Epic Clarity data from on-premises was copied to a virtual network in Microsoft Azure. Three sequential schemas were developed. The Filtered Schema added a filter to retain only SickKids and valid patients. The Curated Schema created a data structure that was easier to navigate and query. Each table contained a logical unit such as patients, hospital encounters or laboratory tests. Data validation of randomly sampled observations in the Curated Schema was performed. The SK-OMOP Schema was designed to facilitate research and machine learning. Two individuals mapped medical elements to standard Observational Medical Outcomes Partnership (OMOP) concepts. Results: A copy of Clarity data was transferred to Microsoft Azure and updated each night using log shipping. The Filtered Schema and Curated Schema were implemented as stored procedures and executed each night with incremental updates or full loads. Data validation required up to 16 iterations for each Curated Schema table. OMOP concept mapping achieved at least 80 % coverage for each SK-OMOP table. Conclusions: We described our experience in creating three sequential schemas to address different EHR data access requirements. Future work should consider replicating this approach at other institutions to determine whether approaches are generalizable.

Self-supervised machine learning using adult inpatient data produces effective models for pediatric clinical prediction tasks.

OBJECTIVE: Development of electronic health records (EHR)-based machine learning models for pediatric inpatients is challenged by limited training data. Self-supervised learning using adult data may be a promising approach to creating robust pediatric prediction models. The primary objective was to determine whether a self-supervised model trained in adult inpatients was noninferior to logistic regression models trained in pediatric inpatients, for pediatric inpatient clinical prediction tasks. MATERIALS AND METHODS: This retrospective cohort study used EHR data and included patients with at least one admission to an inpatient unit. One admission per patient was randomly selected. Adult inpatients were 18 years or older while pediatric inpatients were more than 28 days and less than 18 years. Admissions were temporally split into training (January 1, 2008 to December 31, 2019), validation (January 1, 2020 to December 31, 2020), and test (January 1, 2021 to August 1, 2022) sets. Primary comparison was a self-supervised model trained in adult inpatients versus count-based logistic regression models trained in pediatric inpatients. Primary outcome was mean area-under-the-receiver-operating-characteristic-curve (AUROC) for 11 distinct clinical outcomes. Models were evaluated in pediatric inpatients. RESULTS: When evaluated in pediatric inpatients, mean AUROC of self-supervised model trained in adult inpatients (0.902) was noninferior to count-based logistic regression models trained in pediatric inpatients (0.868) (mean difference = 0.034, 95% CI=0.014-0.057; P < .001 for noninferiority and P = .006 for superiority). CONCLUSIONS: Self-supervised learning in adult inpatients was noninferior to logistic regression models trained in pediatric inpatients. This finding suggests transferability of self-supervised models trained in adult patients to pediatric patients, without requiring costly model retraining.

EHR foundation models improve robustness in the presence of temporal distribution shift.

Temporal distribution shift negatively impacts the performance of clinical prediction models over time. Pretraining foundation models using self-supervised learning on electronic health records (EHR) may be effective in acquiring informative global patterns that can improve the robustness of task-specific models. The objective was to evaluate the utility of EHR foundation models in improving the in-distribution (ID) and out-of-distribution (OOD) performance of clinical prediction models. Transformer- and gated recurrent unit-based foundation models were pretrained on EHR of up to 1.8 M patients (382 M coded events) collected within pre-determined year groups (e.g., 2009-2012) and were subsequently used to construct patient representations for patients admitted to inpatient units. These representations were used to train logistic regression models to predict hospital mortality, long length of stay, 30-day readmission, and ICU admission. We compared our EHR foundation models with baseline logistic regression models learned on count-based representations (count-LR) in ID and OOD year groups. Performance was measured using area-under-the-receiver-operating-characteristic curve (AUROC), area-under-the-precision-recall curve, and absolute calibration error. Both transformer and recurrent-based foundation models generally showed better ID and OOD discrimination relative to count-LR and often exhibited less decay in tasks where there is observable degradation of discrimination performance (average AUROC decay of 3% for transformer-based foundation model vs. 7% for count-LR after 5-9 years). In addition, the performance and robustness of transformer-based foundation models continued to improve as pretraining set size increased. These results suggest that pretraining EHR foundation models at scale is a useful approach for developing clinical prediction models that perform well in the presence of temporal distribution shift.

Evaluation of Feature Selection Methods for Preserving Machine Learning Performance in the Presence of Temporal Dataset Shift in Clinical Medicine.

BACKGROUND: Temporal dataset shift can cause degradation in model performance as discrepancies between training and deployment data grow over time. The primary objective was to determine whether parsimonious models produced by specific feature selection methods are more robust to temporal dataset shift as measured by out-of-distribution (OOD) performance, while maintaining in-distribution (ID) performance. METHODS: Our dataset consisted of intensive care unit patients from MIMIC-IV categorized by year groups (2008-2010, 2011-2013, 2014-2016, and 2017-2019). We trained baseline models using L2-regularized logistic regression on 2008-2010 to predict in-hospital mortality, long length of stay (LOS), sepsis, and invasive ventilation in all year groups. We evaluated three feature selection methods: L1-regularized logistic regression (L1), Remove and Retrain (ROAR), and causal feature selection. We assessed whether a feature selection method could maintain ID performance (2008-2010) and improve OOD performance (2017-2019). We also assessed whether parsimonious models retrained on OOD data performed as well as oracle models trained on all features in the OOD year group. RESULTS: The baseline model showed significantly worse OOD performance with the long LOS and sepsis tasks when compared with the ID performance. L1 and ROAR retained 3.7 to 12.6% of all features, whereas causal feature selection generally retained fewer features. Models produced by L1 and ROAR exhibited similar ID and OOD performance as the baseline models. The retraining of these models on 2017-2019 data using features selected from training on 2008-2010 data generally reached parity with oracle models trained directly on 2017-2019 data using all available features. Causal feature selection led to heterogeneous results with the superset maintaining ID performance while improving OOD calibration only on the long LOS task. CONCLUSIONS: While model retraining can mitigate the impact of temporal dataset shift on parsimonious models produced by L1 and ROAR, new methods are required to proactively improve temporal robustness.

Perspective Toward Machine Learning Implementation in Pediatric Medicine: Mixed Methods Study.

BACKGROUND: Given the costs of machine learning implementation, a systematic approach to prioritizing which models to implement into clinical practice may be valuable. OBJECTIVE: The primary objective was to determine the health care attributes respondents at 2 pediatric institutions rate as important when prioritizing machine learning model implementation. The secondary objective was to describe their perspectives on implementation using a qualitative approach. METHODS: In this mixed methods study, we distributed a survey to health system leaders, physicians, and data scientists at 2 pediatric institutions. We asked respondents to rank the following 5 attributes in terms of implementation usefulness: the clinical problem was common, the clinical problem caused substantial morbidity and mortality, risk stratification led to different actions that could reasonably improve patient outcomes, reducing physician workload, and saving money. Important attributes were those ranked as first or second most important. Individual qualitative interviews were conducted with a subsample of respondents. RESULTS: Among 613 eligible respondents, 275 (44.9%) responded. Qualitative interviews were conducted with 17 respondents. The most common important attributes were risk stratification leading to different actions (205/275, 74.5%) and clinical problem causing substantial morbidity or mortality (177/275, 64.4%). The attributes considered least important were reducing physician workload and saving money. Qualitative interviews consistently prioritized implementations that improved patient outcomes. CONCLUSIONS: Respondents prioritized machine learning model implementation where risk stratification would lead to different actions and clinical problems that caused substantial morbidity and mortality. Implementations that improved patient outcomes were prioritized. These results can help provide a framework for machine learning model implementation.

Do motor plans affect sensorimotor state estimates during temporal decision-making with crossed vs. uncrossed hands? Failure to replicate the dynamic crossed-hand effect.

Hermosillo et al. (J Neurosci 31: 10019-10022, 2011) have suggested that action planning of hand movements impacts decisions about the temporal order judgments regarding vibrotactile stimulation of the hands. Specifically, these authors reported that the crossed-hand effect, a confusion about which hand is which when held in a crossed posture, gradually reverses some 320 ms before the arms begin to move from an uncrossed to a crossed posture or vice versa, such that the crossed-hand is reversed at the time of movement onset in anticipation of the movement's end position. However, to date, no other study has attempted to replicate this dynamic crossed-hand effect. Therefore, in the present study, we conducted four experiments to revisit the question whether preparing uncrossed-to-crossed or crossed-to-uncrossed movements affects the temporo-spatial perception of tactile stimulation of the hands. We used a temporal order judgement (TOJ) task at different time stages during action planning to test whether TOJs are more difficult with crossed than uncrossed hands ("static crossed-hand effect") and, crucially, whether planning to cross or uncross the hands shows the opposite pattern of difficulties ("dynamic crossed-hand effect"). As expected, our results confirmed the static crossed-hand effect. However, the dynamic crossed-hand effect could not be replicated. In addition, we observed that participants delayed their movements with late somatosensory stimulation from the TOJ task, even when the stimulations were meaningless, suggesting that the TOJ task resulted in cross-modal distractions. Whereas the current findings are not inconsistent with a contribution of motor signals to posture perception, they cast doubt on observations that motor signals impact state estimates well before movement onset.

Evaluation of domain generalization and adaptation on improving model robustness to temporal dataset shift in clinical medicine.

Temporal dataset shift associated with changes in healthcare over time is a barrier to deploying machine learning-based clinical decision support systems. Algorithms that learn robust models by estimating invariant properties across time periods for domain generalization (DG) and unsupervised domain adaptation (UDA) might be suitable to proactively mitigate dataset shift. The objective was to characterize the impact of temporal dataset shift on clinical prediction models and benchmark DG and UDA algorithms on improving model robustness. In this cohort study, intensive care unit patients from the MIMIC-IV database were categorized by year groups (2008-2010, 2011-2013, 2014-2016 and 2017-2019). Tasks were predicting mortality, long length of stay, sepsis and invasive ventilation. Feedforward neural networks were used as prediction models. The baseline experiment trained models using empirical risk minimization (ERM) on 2008-2010 (ERM[08-10]) and evaluated them on subsequent year groups. DG experiment trained models using algorithms that estimated invariant properties using 2008-2016 and evaluated them on 2017-2019. UDA experiment leveraged unlabelled samples from 2017 to 2019 for unsupervised distribution matching. DG and UDA models were compared to ERM[08-16] models trained using 2008-2016. Main performance measures were area-under-the-receiver-operating-characteristic curve (AUROC), area-under-the-precision-recall curve and absolute calibration error. Threshold-based metrics including false-positives and false-negatives were used to assess the clinical impact of temporal dataset shift and its mitigation strategies. In the baseline experiments, dataset shift was most evident for sepsis prediction (maximum AUROC drop, 0.090; 95% confidence interval (CI), 0.080-0.101). Considering a scenario of 100 consecutively admitted patients showed that ERM[08-10] applied to 2017-2019 was associated with one additional false-negative among 11 patients with sepsis, when compared to the model applied to 2008-2010. When compared with ERM[08-16], DG and UDA experiments failed to produce more robust models (range of AUROC difference, - 0.003 to 0.050). In conclusion, DG and UDA failed to produce more robust models compared to ERM in the setting of temporal dataset shift. Alternate approaches are required to preserve model performance over time in clinical medicine.

Multivariate Analysis of Electrophysiological Signals Reveals the Time Course of Precision Grasps Programs: Evidence for Nonhierarchical Evolution of Grasp Control.

Current understanding of the neural processes underlying human grasping suggests that grasp computations involve gradients of higher to lower level representations and, relatedly, visual to motor processes. However, it is unclear whether these processes evolve in a strictly canonical manner from higher to intermediate and to lower levels given that this knowledge importantly relies on functional imaging, which lacks temporal resolution. To examine grasping in fine temporal detail here we used multivariate EEG analysis. We asked participants to grasp objects while controlling the time at which crucial elements of grasp programs were specified. We first specified the orientation with which participants should grasp objects, and only after a delay we instructed participants about which effector to use to grasp, either the right or the left hand. We also asked participants to grasp with both hands because bimanual and left-hand grasping share intermediate-level grasp representations. We observed that grasp programs evolved in a canonical manner from visual representations, which were independent of effectors to motor representations that distinguished between effectors. However, we found that intermediate representations of effectors that partially distinguished between effectors arose after representations that distinguished among all effector types. Our results show that grasp computations do not proceed in a strictly hierarchically canonical fashion, highlighting the importance of the fine temporal resolution of EEG for a comprehensive understanding of human grasp control.SIGNIFICANCE STATEMENT A long-standing assumption of the grasp computations is that grasp representations progress from higher to lower level control in a regular, or canonical, fashion. Here, we combined EEG and multivariate pattern analysis to characterize the temporal dynamics of grasp representations while participants viewed objects and were subsequently cued to execute an unimanual or bimanual grasp. Interrogation of the temporal dynamics revealed that lower level effector representations emerged before intermediate levels of grasp representations, thereby suggesting a partially noncanonical progression from higher to lower and then to intermediate level grasp control.

Systematic Review of Approaches to Preserve Machine Learning Performance in the Presence of Temporal Dataset Shift in Clinical Medicine.

OBJECTIVE: The change in performance of machine learning models over time as a result of temporal dataset shift is a barrier to machine learning-derived models facilitating decision-making in clinical practice. Our aim was to describe technical procedures used to preserve the performance of machine learning models in the presence of temporal dataset shifts. METHODS: Studies were included if they were fully published articles that used machine learning and implemented a procedure to mitigate the effects of temporal dataset shift in a clinical setting. We described how dataset shift was measured, the procedures used to preserve model performance, and their effects. RESULTS: Of 4,457 potentially relevant publications identified, 15 were included. The impact of temporal dataset shift was primarily quantified using changes, usually deterioration, in calibration or discrimination. Calibration deterioration was more common (n = 11) than discrimination deterioration (n = 3). Mitigation strategies were categorized as model level or feature level. Model-level approaches (n = 15) were more common than feature-level approaches (n = 2), with the most common approaches being model refitting (n = 12), probability calibration (n = 7), model updating (n = 6), and model selection (n = 6). In general, all mitigation strategies were successful at preserving calibration but not uniformly successful in preserving discrimination. CONCLUSION: There was limited research in preserving the performance of machine learning models in the presence of temporal dataset shift in clinical medicine. Future research could focus on the impact of dataset shift on clinical decision making, benchmark the mitigation strategies on a wider range of datasets and tasks, and identify optimal strategies for specific settings.

Grasping of Real-World Objects Is Not Biased by Ensemble Perception.

The visual system is known to extract summary representations of visually similar objects which bias the perception of individual objects toward the ensemble average. Although vision plays a large role in guiding action, less is known about whether ensemble representation is informative for action. Motor behavior is tuned to the veridical dimensions of objects and generally considered resistant to perceptual biases. However, when the relevant grasp dimension is not available or is unconstrained, ensemble perception may be informative to behavior by providing gist information about surrounding objects. In the present study, we examined if summary representations of a surrounding ensemble display influenced grip aperture and orientation when participants reached-to-grasp a central circular target which had an explicit size but importantly no explicit orientation that the visuomotor system could selectively attend to. Maximum grip aperture and grip orientation were not biased by ensemble statistics during grasping, although participants were able to perceive and provide manual estimations of the average size and orientation of the ensemble display. Support vector machine classification of ensemble statistics achieved above-chance classification accuracy when trained on kinematic and electromyography data of the perceptual but not grasping conditions, supporting our univariate findings. These results suggest that even along unconstrained grasping dimensions, visually-guided behaviors toward real-world objects are not biased by ensemble processing.

Multivariate Analysis of Electrophysiological Signals Reveals the Temporal Properties of Visuomotor Computations for Precision Grips.

The frontoparietal networks underlying grasping movements have been extensively studied, especially using fMRI. Accordingly, whereas much is known about their cortical locus much less is known about the temporal dynamics of visuomotor transformations. Here, we show that multivariate EEG analysis allows for detailed insights into the time course of visual and visuomotor computations of precision grasps. Male and female human participants first previewed one of several objects and, upon its reappearance, reached to grasp it with the thumb and index finger along one of its two symmetry axes. Object shape classifiers reached transient accuracies of 70% at ∼105 ms, especially based on scalp sites over visual cortex, dropping to lower levels thereafter. Grasp orientation classifiers relied on a system of occipital-to-frontal electrodes. Their accuracy rose concurrently with shape classification but ramped up more gradually, and the slope of the classification curve predicted individual reaction times. Further, cross-temporal generalization revealed that dynamic shape representation involved early and late neural generators that reactivated one another. In contrast, grasp computations involved a chain of generators attaining a sustained state about 100 ms before movement onset. Our results reveal the progression of visual and visuomotor representations over the course of planning and executing grasp movements.SIGNIFICANCE STATEMENT Grasping an object requires the brain to perform visual-to-motor transformations of the object's properties. Although much of the neuroanatomic basis of visuomotor transformations has been uncovered, little is known about its time course. Here, we orthogonally manipulated object visual characteristics and grasp orientation, and used multivariate EEG analysis to reveal that visual and visuomotor computations follow similar time courses but display different properties and dynamics.

Emergent Synergistic Grasp-Like Behavior in a Visuomotor Joint Action Task: Evidence for Internal Forward Models as Building Blocks of Human Interactions.

Central to the mechanistic understanding of the human mind is to clarify how cognitive functions arise from simpler sensory and motor functions. A longstanding assumption is that forward models used by sensorimotor control to anticipate actions also serve to incorporate other people's actions and intentions, and give rise to sensorimotor interactions between people, and even abstract forms of interactions. That is, forward models could aid core aspects of human social cognition. To test whether forward models can be used to coordinate interactions, here we measured the movements of pairs of participants in a novel joint action task. For the task they collaborated to lift an object, each of them using fingers of one hand to push against the object from opposite sides, just like a single person would use two hands to grasp the object bimanually. Perturbations of the object were applied randomly as they are known to impact grasp-specific movement components in common grasping tasks. We found that co-actors quickly learned to make grasp-like movements with grasp components that showed coordination on average based on action observation of peak deviation and velocity of their partner's trajectories. Our data suggest that co-actors adopted pre-existing bimanual grasp programs for their own body to use forward models of their partner's effectors. This is consistent with the long-held assumption that human higher-order cognitive functions may take advantage of sensorimotor forward models to plan social behavior. New and Noteworthy: Taking an approach of sensorimotor neuroscience, our work provides evidence for a long-held belief that the coordination of physical as well as abstract interactions between people originates from certain sensorimotor control processes that form mental representations of people's bodies and actions, called forward models. With a new joint action paradigm and several new analysis approaches we show that, indeed, people coordinate each other's interactions based on forward models and mutual action observation.