Decoding Trans-Saccadic Prediction Error.

We are constantly sampling our environment by moving our eyes, but our subjective experience of the world is stable and constant. Stimulus displacement during or shortly after a saccade often goes unnoticed, a phenomenon called the saccadic suppression of displacement. Although we fail to notice such displacements, our oculomotor system computes the prediction errors and adequately adjusts the gaze and future saccadic execution, a phenomenon known as saccadic adaptation. In the present study, we aimed to find a brain signature of the trans-saccadic prediction error that informs the motor system but not explicit perception. We asked participants (either sex) to report whether a visual target was displaced during a saccade while recording electroencephalography (EEG). Using multivariate pattern analysis, we were able to differentiate displacements from no displacements, even when participants failed to report the displacement. In other words, we found that trans-saccadic prediction error is represented in the EEG signal 100 ms after the displacement presentation, mainly in occipital and parieto-occipital channels, even in the absence of explicit perception of the displacement.SIGNIFICANCE STATEMENT Stability in vision occurs even while performing saccades. One suggested mechanism for this counterintuitive visual phenomenon is that external displacement is suppressed during the retinal remapping caused by a saccade. Here, we shed light on the mechanisms of trans-saccadic stability by showing that displacement information is not entirely suppressed and specifically present in the early stages of visual processing. Such a signal is relevant and computed for oculomotor adjustment despite being neglected for perception.

What over When in causal agency: Causal experience prioritizes outcome prediction over temporal priority.

Prior expectations strongly structure the way we perceive the world and ourselves. For instance, action-outcome prediction can modulate time perception and causal experience. We designed a study that allowed us to investigate whether action-outcome prediction has similar effects on time perception and intentional causality. Participants viewed a stimulus that was consistent or inconsistent with the action they, or another agent executed. The stimulus preceded or followed these actions and participants reported simultaneity or causal judgments. Observers were more likely to report the consistent outcomes as being generated by the action, even when the outcomes actually preceded the action. However, outcome consistency did not modulate simultaneity judgments. These results shed insight on the relationship between time and causal experience. It suggests that time perception and causal experience do not rely in the same way on temporal information, the latter being more permeable to contextual cues such as action-outcome consistency.

Action co-representation and the sense of agency during a joint Simon task: Comparing human and machine co-agents.

Recent studies have suggested that individuals are not able to develop a sense of joint agency during joint actions with artificial systems. We sought to examine whether this lack of joint agency is linked to individuals' inability to co-represent the machine-generated actions. Fifteen participants observed or performed a Simon response time task either individually, or jointly with another human or a computer. Participants reported the time interval between their response (or the co-actor response) and a subsequent auditory stimulus, which served as an implicit measure of participants' sense of agency. Participants' reaction times showed a classical Simon effect when they were partnered with another human, but not when they collaborated with a computer. Furthermore, participants showed a vicarious sense of agency when co-acting with another human agent but not with a computer. This absence of vicarious sense of agency during human-computer interactions and the relation with action co-representation are discussed.

Precursor processes of human self-initiated action.

A gradual buildup of electrical potential over motor areas precedes self-initiated movements. Recently, such "readiness potentials" (RPs) were attributed to stochastic fluctuations in neural activity. We developed a new experimental paradigm that operationalized self-initiated actions as endogenous 'skip' responses while waiting for target stimuli in a perceptual decision task. We compared these to a block of trials where participants could not choose when to skip, but were instead instructed to skip. Frequency and timing of motor action were therefore balanced across blocks, so that conditions differed only in how the timing of skip decisions was generated. We reasoned that across-trial variability of EEG could carry as much information about the source of skip decisions as the mean RP. EEG variability decreased more markedly prior to self-initiated compared to externally-triggered skip actions. This convergence suggests a consistent preparatory process prior to self-initiated action. A leaky stochastic accumulator model could reproduce this convergence given the additional assumption of a systematic decrease in input noise prior to self-initiated actions. Our results may provide a novel neurophysiological perspective on the topical debate regarding whether self-initiated actions arise from a deterministic neurocognitive process, or from neural stochasticity. We suggest that the key precursor of self-initiated action may manifest as a reduction in neural noise.

NICU Network Neurobehavioral Scale: 1-month normative data and variation from birth to 1 month.

BackgroundThe Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) is a standardized method for infant neurobehavioral assessment. Normative values are available for newborns, but the NNNS is not always feasible at birth. Unfortunately, 1-month NNNS normative data are lacking.AimsTo provide normative data for the NNNS examination at 1 month and to assess birth-to-one-month changes in NNNS summary scores.Study designThe NNNS was administered at birth and at 1 month within a longitudinal prospective study design.SubjectsA cohort of 99 clinically healthy full-term infants were recruited from a well-child nursery.Outcome measuresBirth-to-1-month NNNS variations were evaluated and the association of neonatal and sociodemographic variables with the rate of change of NNNS summary scores were investigated.Results and conclusionsNNNS scores from the 10th to the 90th percentile represent a range of normative performance at 1 month. A complex pattern of stability and change emerged comparing NNNS summary scores from birth to 1 month. Orienting, Regulation, and Quality of movements significantly increased, whereas Lethargy and Hypotonicity significantly decreased. Birth-to-1-month changes in NNNS performance suggest improvements in neurobehavioral organization. These data are useful for research purposes and for clinical evaluation of neurobehavioral performance in both healthy and at-risk 1-month-old infants.

Specificity of action selection modulates the perceived temporal order of action and sensory events.

The perceived temporal order of actions and changes in the environment is crucial for our inferences of causality. Sensory events presented shortly after an action are more likely considered as self-generated compared to the same events occurring before action execution. However, the estimation of when an action or a sensory change occurred is a challenge for the human brain. This estimation is formed from available sensory information combined with internal representations. Researchers suggested that internal signals associated with action preparation drive our awareness of initiating an action. This study aimed to directly investigate this hypothesis. Participants performed a speeded action (left or right key-press) in response to a go-signal (left or right arrow). A flash was presented at different time points around the time of the action, and participants judged whether it was simultaneous with the action or not. To investigate the role of action preparation in time perception, we compared trials where a cue indicated which action to perform in response to a later go signal presentation, and trials with a neutral cue where participants did not know until the time of the go signal which action to perform. We observed that a flash presented before the action was reported as simultaneous with the action more frequently when actions were cued than when they were uncued. This difference was not observed when the action was replaced by a tactile stimulation. These results indicate that precued actions are experienced earlier in time compared to unprepared actions. Further, this difference is not due to mere non-motor expectation of an event. The experience of initiating an action is driven by action preparation process: when we know what to do, actions are perceived ahead of time.

Agency alters perceptual decisions about action-outcomes.

Humans experience themselves as agents, capable of controlling their actions and the outcomes they generate (i.e., the sense of agency). Inferences of agency are not infallible. Research shows that we often attribute outcomes to our agency even though they are caused by another agent. Moreover, agents report the sensory events they generate to be less intense compared to the events that are generated externally. These effects have been assessed using highly suprathreshold stimuli and subjective measurements. Consequently, it remains unclear whether experiencing oneself as an agent lead to a decision criterion change and/or a sensitivity change. Here, we investigate this issue. Participants were told that their key presses generated an upward dot motion but that on 30 % of the trials the computer would take over and display a downward motion. The upward/downward dot motion was presented at participant's discrimination threshold. Participants were asked to indicate whether they (upward motion) or the computer (downward motion) generated the motion. This group of participants was compared with a 'no-agency' group who performed the same task except that subjects did not execute any actions to generate the dot motion. We observed that the agency group reported seeing more frequently the motion they expected to generate (i.e., upward motion) than the no-agency group. This suggests that agency distorts our experience of (allegedly) caused events by altering perceptual decision processes, so that, in ambiguous contexts, externally generated events are experienced as the outcomes of one's actions.

The prediction of visual stimuli influences auditory loudness discrimination.

The brain combines information from different senses to improve performance on perceptual tasks. For instance, auditory processing is enhanced by the mere fact that a visual input is processed simultaneously. However, the sensory processing of one modality is itself subject to diverse influences. Namely, perceptual processing depends on the degree to which a stimulus is predicted. The present study investigated the extent to which the influence of one processing pathway on another pathway depends on whether or not the stimulation in this pathway is predicted. We used an action-effect paradigm to vary the match between incoming and predicted visual stimulation. Participants triggered a bimodal stimulus composed of a Gabor and a tone. The Gabor was either congruent or incongruent compared to an action-effect association that participants learned in an acquisition phase.We tested the influence of action-effect congruency on the loudness perception of the tone. We observed that an incongruent-task-irrelevant Gabor stimulus increases participant's sensitivity to loudness discrimination. An identical result was obtained for a second condition in which the visual stimulus was predicted by a cue instead of an action. Our results suggest that prediction error is a driving factor of the crossmodal interplay between vision and audition.

Making precise movements increases confidence in perceptual decisions.

Perceptual decision-making often lacks explicit feedback, making confidence in our choices pivotal for guiding subsequent actions. Recent studies have highlighted the role of motor responses in modulating decision confidence. Two competing mechanisms have been proposed to elucidate this phenomenon. The "fluency hypothesis" posits that the ease and smoothness of executing a motor response can serve as a cue to enhance retrospective confidence. Conversely, the "monitoring hypothesis" suggests that the extent of action monitoring during response selection may boost retrospective confidence, with heightened monitoring potentially offsetting response fluency. We conducted a pre-registered experiment to directly test these hypotheses. Participants engaged in a perceptual task involving the discrimination of Gabor patch orientation. Perceptual responses required high or low motor precision, manipulated by the size of target circles that participants had to reach with the computer mouse to provide a response. Contrary to the "fluency hypothesis", our results showed that, in trials requiring higher precision (utilizing small circles), participants reported higher confidence levels compared to trials with less demanding responses (involving larger circles). Importantly, this increase in confidence did not coincide with any change in perceptual accuracy. These findings align with the "monitoring hypothesis," suggesting that the degree of action monitoring during response execution can indeed influence retrospective decision confidence.

What the eyes, confidence, and partner's identity can tell about change of mind.

Perceptual confidence reflects the ability to evaluate the evidence that supports perceptual decisions. It is thought to play a critical role in guiding decision-making. However, only a few empirical studies have actually investigated the function of perceptual confidence. To address this issue, we designed a perceptual task in which participants provided a confidence judgment on the accuracy of their perceptual decision. Then, they viewed the response of a machine or human partner, and they were instructed to decide whether to keep or change their initial response. We observed that confidence predicted participants' changes of mind more than task difficulty and perceptual accuracy. Additionally, interacting with a machine, compared to a human, decreased confidence and increased participants tendency to change their initial decision, suggesting that both confidence and changes of mind are influenced by contextual factors, such as the identity of a partner. Finally, variations in confidence judgments but not change of mind were correlated with pre-response pupil dynamics, indicating that arousal changes are linked to confidence computations. This study contributes to our understanding of the factors influencing confidence and changes of mind and also evaluates the possibility of using pupil dynamics as a proxy of confidence.

Attenuation of auditory N1 results from identity-specific action-effect prediction.

The auditory N1 event-related potential has previously been observed to be attenuated for tones that are triggered by human actions. This attenuation is thought to be generated by motor prediction mechanisms and is considered to be important for agency attribution. The present study was designed to rigorously test the notion of action prediction-based sensory attenuation. Participants performed one of four voluntary actions on each trial, with each button associated with either predictable or unpredictable action effects. In addition, actions with each hand could result in action effects that were either congruent or incongruent with hand-specific prediction. We observed no significant differences in N1 amplitude between predictable and unpredictable tones. When contrasting action effects that were congruent or incongruent with hand-specific prediction, we observed significant attenuation for prediction-congruent compared to prediction-incongruent action-effects. These novel findings suggest that accurate action-effect prediction drives sensory attenuation of auditory stimuli. These findings have important implications for understanding the mechanisms of action-effect prediction and sensory attenuation, and may have clinical implications for studies investigating action awareness and agency in schizophrenia.

Flash glucose monitoring in type 2 diabetes managed with basal insulin in the USA: a retrospective real-world chart review study and meta-analysis.

INTRODUCTION: Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear. This real-world study aimed to assess the impact on glycated hemoglobin (HbA1c) of flash glucose monitoring use in adults with type 2 diabetes managed with basal insulin. RESEARCH DESIGN AND METHODS: Medical records were reviewed for adult individuals with type 2 diabetes using basal insulin for ≥1 year with or without additional antihyperglycemic medication, HbA1c 8.0%-12.0% prior to FreeStyle Libre Flash Glucose Monitoring use for ≥90 days and an HbA1c measurement recorded between 90 and 194 days after device use. Exclusion criteria included utilization of bolus insulin. Meta-analysis data are from the current study (USA) and a similar Canadian cohort. RESULTS: Medical record analysis (n=100) from 8 USA study sites showed significant HbA1c decrease of 1.4%±1.3%, from 9.4%±1.0% at baseline to 8.0%±1.2% after device use, p<0.0001 (mean±SD).Meta-analysis of medical records from USA and Canada sites (n=191) showed HbA1c significantly decreased by 1.1%±0.14% (mean±SE), from baseline 9.2%±1.0% to 8.1%±1.1%, p≤0.0001, with moderate to high heterogeneity between sites (Q=43.9, I2=74.9, p<0.0001) explained by differences in baseline HbA1c between sites.The HbA1c improvement in both groups was observed by age group, body mass index, duration of insulin use and sex at birth. CONCLUSIONS: In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of flash glucose monitoring technology.

On the influence of causal beliefs on the feeling of agency.

The sense of agency is the experience of being the origin of a sensory consequence. This study investigates whether contextual beliefs modulate low-level sensorimotor processes which contribute to the emergence of the sense of agency. We looked at the influence of causal beliefs on 'intentional binding', a phenomenon which accompanies self-agency. Participants judged the onset-time of either an action or a sound which followed the action. They were induced to believe that the tone was either triggered by themselves or by somebody else, although, in reality, the sound was always triggered by the participants. We found that intentional binding was stronger when participants believed that they triggered the tone, compared to when they believed that another person triggered the tone. These results suggest that high-level contextual information influences sensorimotor processes responsible for generating intentional binding.

Metformin dosage patterns in type 2 diabetes patients in a real-world setting in the United States.

AIM: To examine metformin dosage patterns among adults with type 2 diabetes in an integrated healthcare system in the US. METHODS: Using electronic medical records, the proportions of patients receiving different initial metformin doses were reported. Proportion of patients receiving ≥1500 mg metformin daily at initiation or within six months after initiation and the associated sociodemographic and clincal factors were examined. RESULTS: The cohort included 715 patients (52.6% female, 64.1% white, and mean age = 57.0 ± 12.7 years). Of these, 31.3% received an initial daily metformin dose of <850 mg, 46.9% received 850-1499 mg, and 21.8% received ≥1500 mg and 244 (34.1%) patients received ≥1500 mg metformin daily at initiation or within six months after initiation. Patients aged 65-79 years (vs. those aged <50 years) and blacks (vs. whites) were less likely and Hispanics (vs. whites) and patients with higher HbA1c before metformin initiation were more likely to receive ≥1500 mg metformin daily at initiation or within six months after initiation. CONCLUSIONS: Study findings suggest a need for efforts to maximize the proportion of eligible patients receiving a recommended metformin dose. Factors impacting metformin dosage identified in the study could be a useful guidance.

Preparing to React: A Behavioral Study on the Interplay between Proactive and Reactive Action Inhibition.

Motor preparation, based on one's goals and expectations, allows for prompt reactions to stimulations from the environment. Proactive and reactive inhibitory mechanisms modulate this preparation and interact to allow a flexible control of responses. In this study, we investigate these two control mechanisms with an ad hoc cued Go/NoGo Simon paradigm in a within-subjects design, and by measuring subliminal motor activities through electromyographic recordings. Go cues instructed participants to prepare a response and wait for target onset to execute it (Go target) or inhibit it (NoGo target). Proactive inhibition keeps the prepared response in check, hence preventing false alarms. Preparing the cue-coherent effector in advance speeded up responses, even when it turned out to be the incorrect effector and reactive inhibition was needed to perform the action with the contralateral one. These results suggest that informative cues allow for the investigation of the interaction between proactive and reactive action inhibition. Partial errors' analysis suggests that their appearance in compatible conflict-free trials depends on cue type and prior preparatory motor activity. Motor preparation plays a key role in determining whether proactive inhibition is needed to flexibly control behavior, and it should be considered when investigating proactive/reactive inhibition.

Irrelevant auditory and tactile signals, but not visual signals, interact with the target onset and modulate saccade latencies.

Saccadic eye movements bring events of interest to the center of the retina, enabling detailed visual analysis. This study explored whether irrelevant auditory (experiments A, B & F), visual (C & D) or tactile signals (E & F) delivered around the onset of a visual target modulates saccade latency. Participants were instructed to execute a quick saccade toward a target stepping left or right from a fixation position. We observed an interaction between auditory beeps or tactile vibrations and the oculomotor reaction that included two components: a warning effect resulting in faster saccades when the signal and the target were presented simultaneously; and a modulation effect with shorter-or longer-latencies when auditory and tactile signals were delivered before-or after-the target onset. Combining both modalities only increased the modulation effect to a limited extent, pointing to a saturation of the multisensory interaction with the motor control. Interestingly, irrelevant visual stimuli (black background or isoluminant noise strips in peripheral vision, flashed for 10 ms) increased saccade latency whether they were presented just before or after target onset. The lack of latency reduction with visual signals suggests that the modulation observed in the auditory and tactile experiments was not related to priming effects but rather to low-level audio- and tactile-visual integration. The increase in saccade latency observed with irrelevant visual stimuli is discussed in relation to saccadic inhibition. Our results demonstrate that signals conveying no information regarding where and when a visual target would appear modulate saccadic reactivity, much like in multisensory temporal binding, but only when these signals come from a different modality.

Decoding the Temporal Dynamics of Covert Spatial Attention Using Multivariate EEG Analysis: Contributions of Raw Amplitude and Alpha Power.

Attention can be oriented in space covertly without the need of eye movements. We used multivariate pattern classification analyses (MVPA) to investigate whether the time course of the deployment of covert spatial attention leading up to the observer's perceptual decision can be decoded from both EEG alpha power and raw activity traces. Decoding attention from these signals can help determine whether raw EEG signals and alpha power reflect the same or distinct features of attentional selection. Using a classical cueing task, we showed that the orientation of covert spatial attention can be decoded by both signals. However, raw activity and alpha power may reflect different features of spatial attention, with alpha power more associated with the orientation of covert attention in space and raw activity with the influence of attention on perceptual processes.

Human susceptibility to social influence and its neural correlates are related to perceived vulnerability to extrinsic morbidity risks.

Humans considerably vary in the degree to which they rely on their peers to make decisions. Why? Theoretical models predict that environmental risks shift the cost-benefit trade-off associated with the exploitation of others' behaviours (public information), yet this idea has received little empirical support. Using computational analyses of behaviour and multivariate decoding of electroencephalographic activity, we test the hypothesis that perceived vulnerability to extrinsic morbidity risks impacts susceptibility to social influence, and investigate whether and how this covariation is reflected in the brain. Data collected from 261 participants tested online revealed that perceived vulnerability to extrinsic morbidity risks is positively associated with susceptibility to follow peers' opinion in the context of a standard face evaluation task. We found similar results on 17 participants tested in the laboratory, and showed that the sensitivity of EEG signals to public information correlates with the participants' degree of vulnerability. We further demonstrated that the combination of perceived vulnerability to extrinsic morbidity with decoding sensitivities better predicted social influence scores than each variable taken in isolation. These findings suggest that susceptibility to social influence is partly calibrated by perceived environmental risks, possibly via a tuning of neural mechanisms involved in the processing of public information.

Impact of Timely Treatment Intensification on Glycemic Goal Achievement in Patients With Type 2 Diabetes Failing Metformin Monotherapy.

Purpose The purpose of the study was to examine the association between timely treatment intensification (TTI) and glycemic goal achievement in patients with type 2 diabetes (T2D) failing metformin monotherapy (MM). Methods This study was set at a large integrated health care system in the United States. The study cohort included T2D patients aged 18 to 85 years who were on MM between January 2009 and September 2013 and had an uncontrolled glycated hemoglobin (A1C) reading (≥8%) after at least 3 months of MM (corresponding date was index date). Secondary analyses were performed using A1C <7% as T2D control. TTI was defined as receipt of an add-on therapy within 180 days after the index date. Impact of TTI on glycemic goal achievement was determined using multivariate Cox proportional hazards regression. Patients were censored at their last A1C reading or health care visit during 2 years after the index date. Results The study cohort consisted of 996 patients, ~58% male and ~59% Caucasian, with a mean age of ~54 (±12) years. TTI was observed in 50.2% of the patients. The rate of glycemic goal achievement was higher in patients with TTI compared with patients without TTI (hazards ratio = 1.632, 95% confidence interval = 1.328-2.006). The results for the secondary analyses were largely consistent with the primary findings. Conclusions TTI positively affected glycemic goal achievement among T2D patients failing MM and could be a useful strategy to increase the currently low proportion of patients with their T2D controlled in the United States.

Patient and Provider Factors Affecting Clinical Inertia in Patients With Type 2 Diabetes on Metformin Monotherapy.

PURPOSE: Our aim was to determine the extent of clinical inertia and the associated patient and provider factors in patients with type 2 diabetes on metformin monotherapy (MM) at a large integrated health care system in the United States. METHODS: The study cohort included patients with type 2 diabetes aged 18 to 85 years, on MM between January 2009 and September 2013, who experienced MM failure (had an uncontrolled glycosylated hemoglobin [HbA1c] reading (≥8.0% [64 mmol/mol]) after at least 90 days of MM). Clinical inertia was defined as absence of treatment intensification with an add-on therapy within 180 days after the MM failure (index date). The impact of patient and provider factors on clinical inertia was determined using generalized estimating equations. FINDINGS: The study cohort consisted of 996 patients; 58% were men and 59% were white, with a mean age of 53 (11.8) years. Of these, 49.8% experienced clinical inertia. Lower HbA1c at index date, absence of liver diseases, absence of renal diseases, and greater provider age were associated with clinical inertia. The clinical inertia rate in a secondary analysis considering HbA1c <7.0% (53 mmol/mol) as glycemic control was 67.9%. Greater patient age, lower HbA1c at index date, greater provider age, and being a primary care physician were associated with clinical inertia. IMPLICATIONS: Considerable clinical inertia rates were observed in our real-world patient population, suggesting the need of interventions to reduce clinical inertia in clinical practice. Information about patient and provider factors affecting clinical inertia provided by this study could help healthcare policymakers plan and implement such interventions.