Estimating body fat distribution - a driver of cardiometabolic health - from silhouette images

Background: Inter-individual variation in fat distribution is increasingly recognized as clinically important but is not routinely assessed in clinical practice because quantification requires medical imaging. Objectives: We hypothesized that a deep learning model trained on an individual's body shape outline - or silhouette - would enable accurate estimation of specific fat depots, including visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes, and VAT/ASAT ratio. We additionally set out to study whether silhouette-estimated VAT/ASAT ratio may stratify risk of cardiometabolic diseases independent of body mass index (BMI) and waist circumference. Methods: Two-dimensional coronal and sagittal silhouettes were constructed from whole-body magnetic resonance images in 40,032 participants of the UK Biobank and used to train a convolutional neural network to predict VAT, ASAT, and GFAT volumes, and VAT/ASAT ratio. Logistic and Cox regressions were used to determine the independent association of silhouette-predicted VAT/ASAT ratio with type 2 diabetes and coronary artery disease. Results: Mean age of the study participants was 65 years and 51% were female. A deep learning model trained on silhouettes enabled accurate estimation of VAT, ASAT, and GFAT volumes (R2: 0.88, 0.93, and 0.93, respectively), outperforming a comparator model combining anthropometric and bioimpedance measures (ΔR2 = 0.05-0.13). Next, we studied VAT/ASAT ratio, a nearly BMI- and waist circumference-independent marker of unhealthy fat distribution. While the comparator model poorly predicted VAT/ASAT ratio (R2: 0.17-0.26), a silhouette-based model enabled significant improvement (R2: 0.50-0.55). Silhouette-predicted VAT/ASAT ratio was associated with increased prevalence of type 2 diabetes and coronary artery disease. Conclusions: Body silhouette images can estimate important measures of fat distribution, laying the scientific foundation for population-based assessment.

The sense of agency does not evidence regulative control

Libertarians assume that the sense of agency supports their belief in the agent’s ability to have done otherwise; however, they do not present arguments in favor of their assumption beyond introspection. Although agents may hold this belief, the mechanisms that give rise to the sense of agency—the comparator model and the perception of the relation between action and events in the environment—do not provide reasons to support it. Nonetheless, these mechanisms can help explain why agents hold the belief in the first place, and the investigation makes clear that the workings of the mechanisms that give rise to the sense of agency are compatible with determinism. Here, I will defend that a compatibilist explanation can be given as to why the sense of agency may seem to support libertarian beliefs. Hence, the sense of agency does not support the libertarian position in the free will debate; it is merely the pre-reflective experience of action as self-caused, and it is associated with control mechanisms.Keywords: Sense of agency, Regulative control, Incompatibilism, Comparator model, Guidance control.

Intentional Binding Effects in the Experience of Noticing the Regularity of a Perceptual-Motor Task

Noticing the regularity of the task is necessary to enhance motor performance. The experience of noticing further motivates improvement in motor performance. Motor control is explained by a comparator model that modifies the motor command to reduce discrepancies between sensory predictions and actual outcomes. A similar model could apply to sense of agency (SoA). SoA refers to the sensation of controlling one’s own actions and, through them, the outcomes in the external world. SoA may also be enhanced by the experience of noticing errors. We recently reported gradual enhancement of SoA in participants with high perceptual-motor performance. However, what component of the motor task changed the SoA is unclear. In this study, we aimed to investigate the influence over time of the experience of noticing during a motor task on SoA. Participants performed an implicit regularity perceptual-motor task and an intentional binding task (a method that can quantitatively measure SoA) simultaneously. We separated participants into groups after the experiment based on noticing or not noticing the regularity. SoA was gradually enhanced in the noticing group, compared with that of the non-noticing group. The results suggest that the experience of noticing may enhance SoA during perceptual-motor tasks.

An International Prospective Cohort Study To Validate 2 Prediction Rules for Infections Caused by Third-generation Cephalosporin-resistant Enterobacterales

Background The possibility of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacterales (3GC-R-BSI) leads to a trade-off between empiric inappropriate treatment (IAT) and unnecessary carbapenem use (UCU). Accurately predicting 3GC-R-BSI could reduce IAT and UCU. We externally validate 2 previously derived prediction rules for community-onset (CO) and hospital-onset (HO) suspected bloodstream infections. Methods In 33 hospitals in 13 countries we prospectively enrolled 200 patients per hospital in whom blood cultures were obtained and intravenous antibiotics with coverage for Enterobacterales were empirically started. Cases were defined as 3GC-R-BSI or 3GC-R gram-negative infection (3GC-R-GNI) (analysis 2); all other outcomes served as a comparator. Model discrimination and calibration were assessed. Impact on carbapenem use was assessed at several cutoff points. Results 4650 CO infection episodes were included and the prevalence of 3GC-R-BSI was 2.1% (n = 97). IAT occurred in 69 of 97 (71.1%) 3GC-R-BSI and UCU in 398 of 4553 non–3GC-R-BSI patients (8.7%). Model calibration was good, and the AUC was .79 (95% CI, .75–.83) for 3GC-R-BSI. The prediction rule potentially reduced IAT to 62% (60/97) while keeping UCU comparable at 8.4% or could reduce UCU to 6.3% (287/4553) while keeping IAT equal. IAT and UCU in all 3GC-R-GNIs (analysis 2) improved at similar percentages. 1683 HO infection episodes were included and the prevalence of 3GC-R-BSI was 4.9% (n = 83). Here model calibration was insufficient. Conclusions A prediction rule for CO 3GC-R infection was validated in an international cohort and could improve empirical antibiotic use. Validation of the HO rule yielded suboptimal performance.

Speaking with an alien voice: Flexible sense of agency during vocal production

Speakers monitor auditory feedback during speech production in order to correct for speech errors. The comparator model proposes that this process is supported by comparing sensory feedback to internal predictions of the sensory consequences of articulation. Additionally, this comparison process is proposed to support the sense of agency over vocal output. The current study tests this hypothesis by asking whether mismatching auditory feedback leads to a decrease in the sense of agency as measured by speakers’ responses to pitch-shifted feedback. Participants vocalized while auditory feedback was unexpectedly and briefly pitch-shifted. In addition, in one block, the entire vocalization’s pitch was baseline-shifted (‘alien voice’), while it was not in the other block (‘normal voice’). Participants compensated for the pitch shifts even in the alien voice condition, suggesting that agency was flexible. This is problematic for the classic comparator model, where a mismatching feedback would lead to a loss of agency. Alternative models are discussed in light of these findings, including an adapted comparator model and the inferential account, which suggests that agency is inferred from the joint contribution of several multisensory sources of evidence. Together, these findings suggest that internal representations of one’s own voice are more flexible than often assumed.

Sensorimotor conflicts induce somatic passivity and louden quiet voices in healthy listeners

Sensorimotor conflicts are known to alter the perception of accompanying sensory signals and deficits in sensory attenuation have been observed in schizophrenia. In the auditory domain, self-generated tones or voices (compared to tones or voices presented passively or with sensorimotor delays) have been associated with changes in loudness perception and attenuated neural responses. It has been argued that for sensory signals to be attenuated, predicted and sensory consequences must have a consistent spatiotemporal relationship, between button presses and reafferent tactile signals, via predictive sensory signaling, a process altered in schizophrenia. Here, we investigated auditory sensory attenuation for a series of morphed voices while healthy participants applied sensorimotor stimulations that had no spatiotemporal relationship to the voice stimuli and that have been shown to induce mild psychosis-like phenomena. In two independent groups of participants, we report a loudening of silent voices and found this effect only during maximal sensorimotor conflicts (versus several control conditions). Importantly, conflicting sensorimotor stimulation also induced a mild psychosis-like state in the form of somatic passivity and participants who experienced stronger passivity lacked the sensorimotor loudening effect. We argue that this conflict-related sensorimotor loudness amplification may represent a reduction of auditory self-attenuation that is lacking in participants experiencing a concomitant mild psychosis-like state. We interpret our results within the framework of the comparator model of sensorimotor control, and discuss the implications of our findings regarding passivity experiences and hallucinations in schizophrenia.

A Delusion of Control - What happens to a sense of Agency in Schizophrenic patients?

The sense of agency is known to be disrupted in Schizophrenia. This article explores the transition from the comparator model to the two-step model of agency, in order to review the paper ‘In and out of control: brain mechanisms linking fluency of action selection to self-agency in patients with Schizophrenia’1. A sense of agency involves using retrospective cues to make causal inferences, but this paper also introduces a new, prospective aspect. This paper shows that subliminal priming, a prospective cue, increases the reported sense of agency over a subsequent action outcome. It also shows that in schizophrenic patients, retrospective cues had more of an influence on their reported sense of agency, while conversely, prospective cues had less influence. This may reflect a greater reliance on retrospective cues in schizophrenia, which could be one of the underlying factors for some of the delusions seen in schizophrenia. Using fMRI measurements during the task, results suggest that angular gyrus activation reflects the experience of non-agency. In healthy controls, they saw altered connectivity between frontal areas and the angular gyrus associated with priming. In schizophrenic patients, there was no effect of priming on activation of the angular gyrus, or frontoparietal connectivity. In our review, we have introduced a putative schema that suggests that the action selection signals from the frontal lobes into the angular gyrus represent the prospective aspect of agency. This connection is disrupted In schizophrenia, and that may be why prospective agency is impaired.

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.