Impact of decision and action outcomes on subsequent decision and action behaviours in humans.

Speed-accuracy trade-off adjustments in decision-making have been mainly studied separately from those in motor control. In the wild, however, animals coordinate their decision and action, often deciding while acting. Recent behavioural studies support this view, indicating that animals, including humans, trade decision time for movement time to maximize their global rate of reward during experimental sessions. Besides, it is well established that choice outcomes impact subsequent decisions. Crucially though, whether and how a decision outcome also influences the subsequent motor performance, and whether and how the outcome of a movement influences the next decision, is unclear. Here, we address these questions by analysing trial-to-trial changes of choice and motor behaviours in healthy human participants instructed to perform successive perceptual decisions expressed with reaching movements whose duration was either weakly or strongly constrained in separate tasks. Results indicate that after a wrong decision, subjects who were weakly constrained in their action duration decided more slowly and more accurately. Interestingly, they also shortened their subsequent movement duration by moving faster. Conversely, we found that errors of constrained movements influenced not only the speed and the amplitude of the following movement but those of the decision too. If the movement had to be slowed down, the decision that precedes that movement was accelerated and vice versa. Together, these results indicate that from one trial to the next, humans seek to determine a behavioural duration as a whole instead of optimizing each of the decision and action speed-accuracy trade-offs independently of each other.

Humans sacrifice decision-making for action execution when a demanding control of movement is required.

A growing body of evidence suggests that decision-making and action execution are governed by partly overlapping operating principles. Especially, previous work proposed that a shared decision urgency/movement vigor signal, possibly computed in the basal ganglia, coordinates both deliberation and movement durations in a way that maximizes the reward rate. Recent data support one aspect of this hypothesis, indicating that the urgency level at which a decision is made influences the vigor of the movement produced to express this choice. Here we investigated whether, conversely, the motor context in which a movement is executed determines decision speed and accuracy. Twenty human subjects performed a probabilistic decision task in which perceptual choices were expressed by reaching movements toward targets whose size and distance from a starting position varied in distinct blocks of trials. We found strong evidence for an influence of the motor context on most of the subjects' decision policy, but contrary to the predictions of the "shared regulation" hypothesis, we observed that slow movements executed in the most demanding motor blocks in terms of accuracy were often preceded by faster and less accurate decisions compared with blocks of trials in which big targets allowed expression of choices with fast and inaccurate movements. These results suggest that decision-making and motor control are not regulated by one unique "invigoration" signal determining both decision urgency and action vigor, but more likely by independent, yet interacting, decision urgency and movement vigor signals.NEW & NOTEWORTHY Recent hypotheses propose that choices and movements share optimization principles derived from economy, possibly implemented by one unique context-dependent regulation signal determining both processes' speed. In the present behavioral study conducted on human subjects, we demonstrate that action properties indeed influence perceptual decision-making, but that decision duration and action vigor are actually independently set depending on the difficulty of the movement executed to report a choice.

Prognostic value of the 12-lead surface electrocardiogram in sarcomeric hypertrophic cardiomyopathy: data from the REMY French register.

AIMS: To identify independent electrocardiogram (ECG) predictors of long-term clinical outcome based on standardized analysis of the surface ECG in a large multicentre cohort of patients with sarcomeric hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Retrospective observational study from the REMY French HCM clinical research observatory. Primary endpoint was a composite of all-cause mortality, major non-fatal arrhythmic events, hospitalization for heart failure (HF), and stroke. Secondary endpoints were components of the primary endpoint. Uni- and multivariable Cox proportional hazard regression analysis was performed to identify independent predictors. Among 994 patients with HCM, only 1.8% had a strictly normal baseline ECG. The most prevalent abnormalities were inverted T waves (63.7%), P-wave abnormalities (30.4%), and abnormal Q waves (25.5%). During a mean follow-up of 4.0 ± 2.0 years, a total of 272 major cardiovascular events occurred in 217 patients (21.8%): death or heart transplant in 98 (9.8%), major arrhythmic events in 40 (4.0%), HF hospitalization in 115 (11.6%), and stroke in 23 (2.3%). At multivariable analysis using ECG covariates, prolonged QTc interval, low QRS voltage, and PVCs of right bundle branch block pattern predicted worse outcome, but none remained independently associated with the primary endpoint after adjustment on main demographic and clinical variables. For secondary endpoints, abnormal Q waves independently predicted all-cause death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.23-4.47; P = 0.009] and prolonged QTc the risk of HF hospitalization (HR 1.006, 95% CI 1.001-1.011; P = 0.024). CONCLUSION: The 12-lead surface ECG has no independent value to predict the primary outcome measure in patients with HCM. The 12-lead surface ECG has been widely used as a screening tool in HCM but its prognostic value remains poorly known. The value of baseline surface ECG to predict long-term clinical outcomes was studied in a cohort of 994 patients with sarcomeric HCM. The surface ECG has no significant additional value to predict outcome in this patient population.

Boosting Norepinephrine Transmission Triggers Flexible Reconfiguration of Brain Networks at Rest.

The locus coeruleus-norepinephrine (LC-NE) system is thought to act as a reset signal allowing brain network reorganization in response to salient information in the environment. However, no direct evidence of NE-dependent whole-brain reorganization has ever been described. We used resting-state functional magnetic resonance imaging in monkeys to investigate the impact of NE-reuptake inhibition on whole-brain connectivity patterns. We found that boosting NE transmission changes functional connectivity between and within resting-state networks. It modulated the functional connectivity pattern of a brainstem network including the LC region and interactions between associative and sensory-motor networks as well as within sensory-motor networks. Among the observed changes, those involving the fronto-parietal attention network exhibited a unique pattern of uncoupling with other sensory-motor networks and correlation switching from negative to positive with the brainstem network that included the LC nucleus. These findings provide the first empirical evidence of NE-dependent large-scale brain network reorganization and further demonstrate that the fronto-parietal attention network represents a central feature within this reorganization.

Hypersynchrony in sarcomeric hypertrophic cardiomyopathy: description and mechanistic approach using multimodal electro-mechanical non-invasive cartography (HSYNC study).

Background: Little is known about left ventricular (LV) sequences of contraction and electrical activation in hypertrophic cardiomyopathy (HCM). A better understanding of the underlying relation between mechanical and electrical activation may allow the identification of predictive response criteria to right ventricular DDD pacing in obstructive patients. Objective: To describe LV mechanical and electrical activation sequences in HCM patients compared to controls. Materials and methods: We prospectively studied, in 40 HCM patients (20 obstructive and 20 non-obstructive) and 20 healthy controls: (1) mechanical activation using echocardiography at rest and cardiac magnetic resonance imaging, (2) electrical activation using 3-dimensional electrocardiographic mapping (ECM). Results: In echocardiography, healthy controls had a physiological apex-to-base delay (ABD) during contraction (23.8 ± 16.2 ms). Among the 40 HCM patients, 18 HCM patients presented a loss of this ABD (<10 ms, defining hypersynchrony) more frequently than controls (45% vs. 5%, p = 0.017). These patients had a lower LV end-diastolic volume (71.4 ± 9.7 ml/m2 vs. 82.4 ± 14.8 ml/m2, p = 0.01), lower native T1 values (988 ± 32 ms vs. 1,028 ± 39 ms, p = 0.001) and tended to have lower LV mass (80.7 ± 23.7 g/m2 vs. 94.5 ± 25.3 g/m2, p = 0.08) compared with HCM patients that had a physiological contraction sequence. There was no significant relation between ABD and LV outflow tract obstruction. While HCM patients with a physiological contraction sequence presented an ECM close to those encountered in controls, patients with a loss of ABD presented a particular pattern of ECM with the first potential more frequently occurring in the postero-basal region. Conclusion: The LV contraction sequence can be modified in HCM patients, with a loss of the physiological ABD, and is associated with smaller LV dimensions and a particular pattern of ECM. Further research is needed to determine whether this pattern is related to an electrical substrate or is the consequence of the hypertrophied heart's specific geometry. Clinical trial registration: ClinicalTrial.gov: NCT02559726.

Venous dysfunction in obstructive hypertrophic cardiomyopathies: Results from the "HCM-Vein" pilot study.

Background: Hypertrophic cardiomyopathies (HCM) can be complicated by left ventricular outflow-tract obstruction (LVOTO) responsible for disabling exercise symptoms, a phenomenon influenced by hemodynamic factors including venous return. Methods: We aimed to evaluate venous dysfunction in obstructive HCM patients compared to healthy controls, and to investigate the relationship between venous dysfunction parameters and LVOTO in HCM. This is a clinical, monocentric, prospective, pilot study, in a tertiary care center. We investigated venous function using venous air plethysmography, and endothelial function. Results: Among the 30 symptomatic obstructive HCM patients, 30% (n = 9) presented abnormal venous residual volume fraction (RVFv) which translates in elevated ambulatory venous pressure vs. 0% in the 10 healthy controls (p < 0.05). Comparing obstructive HCM patients with abnormal RVFv (n = 9) to other obstructive HCM patients with normal RVFv (n = 21), there were no significant differences in terms of age, sex (67% male), and classical echocardiographic parameters both at rest and during exercise, except for left ventricular end-diastolic volume index which was significantly lower in the group with abnormal RVFv compared to the other HCM patients (40.1 ± 9.0 ml/m2 vs. 50.2 ± 10.6 ml/m2, p = 0.01). Fifty six percent of obstructive HCM patients with abnormal RVFv had an absolute increase in Willebrand factor (vs. 26% of other obstructive HCM patients, p < 0.05). Conclusions: In this pilot monocentric study, venous insufficiency was observed in about 30% of symptomatic obstructive HCM patients. Patients with venous insufficiency had more frequently a smaller LV cavity volume. Due to the small sample size, this study is only hypothesis-generating, and further investigations are needed.

Dissociating the Impact of Movement Time and Energy Costs on Decision-Making and Action Initiation in Humans.

Recent theories and data suggest that adapted behavior involves economic computations during which multiple trade-offs between reward value, accuracy requirement, energy expenditure, and elapsing time are solved so as to obtain rewards as soon as possible while spending the least possible amount of energy. However, the relative impact of movement energy and duration costs on perceptual decision-making and movement initiation is poorly understood. Here, we tested 31 healthy subjects on a perceptual decision-making task in which they executed reaching movements to report probabilistic choices. In distinct blocks of trials, the reaching duration ("Time" condition) and energy ("Effort" condition) costs were independently varied compared to a "Reference" block, while decision difficulty was maintained similar at the block level. Participants also performed a simple delayed-reaching (DR) task aimed at estimating movement initiation duration in each motor condition. Results in that DR task show that long duration movements extended reaction times (RTs) in most subjects, whereas energy-consuming movements led to mixed effects on RTs. In the decision task, about half of the subjects decreased their decision durations (DDs) in the Time condition, while the impact of energy on DDs were again mixed across subjects. Decision accuracy was overall similar across motor conditions. These results indicate that movement duration and, to a lesser extent, energy expenditure, idiosyncratically affect perceptual decision-making and action initiation. We propose that subjects who shortened their choices in the time-consuming condition of the decision task did so to limit a drop of reward rate.

Atomoxetine modulates the contribution of low-level signals during free viewing of natural images in rhesus monkeys.

Visuo-spatial attentional orienting is fundamental to selectively process behaviorally relevant information, depending on both low-level visual attributes of stimuli in the environment and higher-level factors, such as goals, expectations and prior knowledge. Growing evidence suggests an impact of the locus-cœruleus-norepinephrine (LC-NE) system in attentional orienting that depends on taskcontext. Nonetheless, most of previous studies used visual displays encompassing a target and various distractors, often preceded by cues to orient the attentional focus. This emphasizes the contribution of goal-driven processes, at the expense of other factors related to the stimulus content. Here, we aimed to determine the impact of NE on attentional orienting in more naturalistic conditions, using complex images and without any explicit task manipulation. We tested the effects of atomoxetine (ATX) injections, a NE reuptake inhibitor, on four monkeys during free viewing of images belonging to three categories: landscapes, monkey faces and scrambled images. Analyses of the gaze exploration patterns revealed, first, that the monkeys spent more time on each fixation under ATX compared to the control condition, regard less of the image content. Second, we found that, depending on the image content, ATX modulated the impact of low-level visual salience on attentional orienting. This effect correlated with the effect of ATX on the number and duration of fixations. Taken together, our results demonstrate that ATX adjusts the contribution of salience on attentional orienting depending on the image content, indicative of its role in balancing the role of stimulus-driven and top-down control during free viewing of complex stimuli.

Peer Presence Effect on Numerosity and Phonological Comparisons in 4th Graders: When Working with a SchoolMate Makes Children More Adult-like.

Little is known about how peers' mere presence may, in itself, affect academic learning and achievement. The present study addresses this issue by exploring whether and how the presence of a familiar peer affects performance in a task assessing basic numeracy and literacy skills: numerosity and phonological comparisons. We tested 99 fourth-graders either alone or with a classmate. Ninety-seven college-aged young adults were also tested on the same task, either alone or with a familiar peer. Peer presence yielded a reaction time (RT) speedup in children, and this social facilitation was at least as important as that seen in adults. RT distribution analyses indicated that the presence of a familiar peer promotes the emergence of adult-like features in children. This included shorter and less variable reaction times (confirmed by an ex-Gaussian analysis), increased use of an optimal response strategy, and, based on Ratcliff's diffusion model, speeded up nondecision (memory and/or motor) processes. Peer presence thus allowed children to at least narrow (for demanding phonological comparisons), and at best, virtually fill in (for unchallenging numerosity comparisons) the developmental gap separating them from adult levels of performance. These findings confirm the influence of peer presence on skills relevant to education and lay the groundwork for exploring how the brain mechanisms mediating this fundamental social influence evolve during development.

Global and regional echocardiographic strain to assess the early phase of hypertrophic cardiomyopathy due to sarcomeric mutations.

AIMS: Hypertrophic cardiomyopathy (HCM) is a genetic disease with delayed cardiac expression. Our objective was to characterize left ventricular (LV) myocardial strain by two-dimensional echocardiography in sarcomeric mutation carriers before the hypertrophic stage. METHODS AND RESULTS: We studied 140 adults [derivation cohort (n = 79), validation cohort (n = 61)]. The derivation cohort comprised 38 confirmed HCM patients with hypertrophy (LVH+/Gen+), 20 mutation carriers without LV hypertrophy (LVH-/Gen+), and 21 healthy controls. LV global longitudinal strain was not different in LVH-/Gen+ compared with controls [20.6%, interquartile (IQ): 18.3/24.2 vs. 22.9%, IQ: 20.9/26.8] but was reduced in LVH+/Gen+ patients (14.1%, IQ: 11.8/18.5, P < 0.001). Regional peak longitudinal strain was significantly decreased in LVH-/Gen+ when compared with controls in four segments: basal anteroseptal (BAS) wall (P = 0.018), basal inferoseptal wall (P = 0.047), basal inferior wall (P = 0.006), and mid anteroseptal wall (P = 0.022). Receiver operating characteristic analysis identified that BAS strain <16.5% had a sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV, NPV) of 57%, 90%, 82%, and 67%, respectively, to differentiate LVH-/G+ patients from controls. Similarly, the accuracy of a ratio between basal inferoseptal/basal anterolateral (BIS/BAL) strain <0.76 was 73%, 92%, 82%, and 64%, respectively (Se/Sp/PPV/NPV). In the validation cohort, the accuracy of BAS and BIS/BAL was 39%/93%/87%/57% and 55%/96%/95%/64% (Se/Sp/PPV/NPV), respectively, to differentiate the LVH-/Gen+ group from controls. CONCLUSION: Regional longitudinal strain, but not global strain, was significantly reduced at the early stage of HCM before LV hypertrophy. This suggests that the inclusion of strain (BAS < 16.5%; BIS/BAL < 0.76) in the evaluation of HCM relatives would help identify mutation carriers and early LV abnormalities.

Characterization of Fabry Disease cardiac involvement according to longitudinal strain, cardiometabolic exercise test, and T1 mapping.

In Anderson-Fabry disease (FD), we sought to evaluate relation between left ventricular (LV) hypertrophy, longitudinal strain (LS), myocardial T1 mapping and cardiopulmonary exercise parameters, and their prognostic value in term of cardiovascular outcomes. In this prospective, observational, monocentric study called "FABRY-Image", we evaluated consecutive adult FD patients by echocardiography, cardiac magnetic resonance, and cardiopulmonary exercise testing. We investigated regional LS, the relations between LV hypertrophy, LS, T1 mapping, and VO2 peak and VE/VCO2, and the prediction of cardiovascular events during follow-up. From 2016 to 2019, we included 35 FD patients (44 ± 17 years, 40% male), that were compared with 20 controls. In FD patients, global, basal and mid-LV LS, as well as mean T1 were significantly altered compared to controls (p < 0.05) with relative apical LS sparing. LV wall thickness was particularly related to mean of basal LS (r = - 0.73), to T1 (r = - 0.48), and to VE/VCO2 (r = 0.45). Mean of basal LS was well related to myocardial T1 (r = 0.59). A good relation was observed between VO2 peak and global LS (r = 0.39) while VE/VCO2 slope was more related to maximal LV wall thickness (r = 0.45), and T1 (r = - 0.61). During a median follow-up of 2.4 years, 6/31 patients presented de novo atrial fibrillation or stroke. In Cox univariate analyses, LV wall thickness, basal LS, T1 value, and VE/VCO2 were significantly predictive of occurrence of de novo atrial fibrillation or stroke (p < 0.05). Our study shows an apical LS sparing in FD patients as observed in amyloidosis, and a close relation between LV hypertrophy, LS, T1 mapping, and VE/VCO2 which are all associated to the occurrence of de novo atrial fibrillation or TIA/stroke during follow-up. These results need to be confirmed by future multicentric studies.

Atomoxetine modulates the relationship between perceptual abilities and response bias.

Elucidation of how neuromodulators influence motivated behaviors is a major challenge of neuroscience research. It has been proposed that the locus-cœruleus-norepinephrine system promotes behavioral flexibility and provides resources required to face challenges in a wide range of cognitive processes. Both theoretical models and computational models suggest that the locus-cœruleus-norepinephrine system tunes neural gain in brain circuits to optimize behavior. However, to the best of our knowledge, empirical proof demonstrating the role of norepinephrine in performance optimization is scarce. Here, we modulated norepinephrine transmission in monkeys performing a Go/No-Go discrimination task using atomoxetine, a norepinephrine-reuptake inhibitor. We tested the optimization hypothesis by assessing perceptual sensitivity, response bias, and their functional relationship within the framework of the signal detection theory. We also manipulated the contingencies of the task (level of stimulus discriminability, target stimulus frequency, and decision outcome values) to modulate the relationship between sensitivity and response bias. We found that atomoxetine increased the subject's perceptual sensitivity to discriminate target stimuli regardless of the task contingency. Atomoxetine also improved the functional relationship between sensitivity and response bias, leading to a closer fit with the optimal strategy in different contexts. In addition, atomoxetine tended to reduce reaction time variability. Taken together, these findings support a role of norepinephrine transmission in optimizing response strategy.

Atomoxetine improves attentional orienting in a predictive context.

The role of norepinephrine (NE) in visuo-spatial attention remains poorly understood. Our goal was to identify the attentional processes influenced by atomoxetine (ATX) injections, a NE-reuptake inhibitor that boosts the level of NE in the brain, and to characterize these influences. We tested the effects of ATX injections, on seven monkeys performing a saccadic cued task in which cues and distractors were used to manipulate spatial attention. We found that when the cue accurately predicted the location of the upcoming cue in 80% of the trials, ATX consistently improved attentional orienting, as measured from reaction times (RTs). These effects were best accounted for by a faster accumulation rate in the valid trials, rather than by a change in the decision threshold. By contrast, the effect of ATX on alerting and distractor interference was more inconsistent. Finally, we also found that, under ATX, RTs to non-cued targets were longer when these were presented separately from cued targets. This suggests that the impact of NE on visuo-spatial attention depends on the context, such that the adaptive changes elicited by the highly informative value of the cues in the most frequent trials were accompanied by a cost in the less frequent trials.

Upright treadmill vs. semi-supine bicycle exercise echocardiography to provoke obstruction in symptomatic hypertrophic cardiomyopathy: a pilot study.

Aims: Recent findings regarding hypertrophic cardiomyopathy (HCM) haemodynamics emphasized the relationship between symptoms, left ventricular outflow tract obstruction (LVOTO), and the preload condition as the venous return level. As various types of exercises have different effects on peripheral vascular beds, this study sought to compare upright treadmill exercise echocardiography (EE) to semi-supine bicycle EE in maximum provoked LVOTO in HCM patients. Methods and results: Semi-supine bicycle and upright treadmill EE were prospectively performed in HCM patients with New York Heart Association functional Class II. Maximal LVOT gradient at rest in the supine and standing position, and during Valsalva manoeuvre, LVOT gradients of both semi-supine bicycle and treadmill exercise at peak and post-exercise, maximal exercise levels, and blood pressure adaptation were recorded. One patient was excluded for not sufficient image quality during treadmill. We studied 22/23 patients (mean age: 54.9 ± 12.3 yrs; 55% male). The supine position at rest displayed a mean maximal LVOT gradient of 46.1 ± 44.8 mmHg, which increased to 51.6 ± 41.2 mmHg during Valsalva (P = 0.066), and to 55.1 ± 37.8 mmHg in the standing position (P = 0.053). Mean maximal peak exercise LVOT gradient with semi-supine bicycle was significantly lower than in treadmill EE (54.6 ± 38.2 mmHg vs. 87.5 ± 42.1 mmHg, respectively, P < 0.01). Among these patients, 41% exhibited LVOT gradient ≥ 30 mmHg at rest. Moreover, 41% exhibited LVOT gradient ≥ 50 mmHg during Valsalva, 55% in resting standing position, 41% at peak semi-supine bicycle exercise, 91% at peak treadmill exercise, and 95% in standing position during treadmill recovery period. Conclusion: This pilot study may suggest treadmill's greater value compared to semi-supine bicycle EE for determining maximum LVOT gradient in HCM.

Characterization of hypertrophic cardiomyopathy according to global, regional, and multi-layer longitudinal strain analysis, and prediction of sudden cardiac death.

To evaluate the severity of hypertrophic cardiomyopathy (HCM) according to global, regional, and multi-layer longitudinal strain (LS) analysis using speckle-tracking echocardiography. From February 2007 to November 2014, we prospectively evaluated 375 consecutive HCM patients referred to our specialized cardiomyopathy center. Demographics, clinical, and rest and exercise echocardiographic parameters were collected according to a completely standardized protocol. Global, regional, and multilayer strain analyses were performed. Correlations between LS and other characteristics were evaluated, and we assessed their prognostic value to predict sudden cardiac death (SCD) or appropriate implantable cardioverter defibrillator (ICD) shocks during follow-up, using Cox proportional hazards analyses. We finally included 217 patients (50.1 ± 15.6 years, 67% male) but only 179 (82%) had LS analysis of sufficient quality. An inverse relation was observed between the mean basal left ventricular (LV) LS and diastolic parameters [E/Ea (r = - 0.30) and left atrium indexed volume (r = - 0.23)], as well as between the resting LV outflow-tract maximal gradient (r = - 0.26) or during peak exercise (r = - 0.20). Mean LS in the LV hypertrophic area was particularly related with maximal wall thickness (r = - 0.47) and transmural global LS with the degree of myocardial fibrosis in cardiac magnetic resonance (r = - 0.32). During a median follow-up of 2.8 ± 1.5 years, mean transmural LS in the hypertrophic area was predictor of SCD and appropriate ICD shock (10 events/179 patients, hazard ratio = 0.83 [95% CI 0.72-0.95], p = 0.01). Basal LS and hypertrophic area LS are valuable parameters to evaluate HCM severity. Mean hypertrophic area LS particularly seems predictive of SCD occurrence and appropriate ICD shocks.

Predictors of future onset of atrial fibrillation in hypertrophic cardiomyopathy.

BACKGROUND: Novel predictors of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) are desirable. AIM: To detect new multimodality imaging variables predictive of de novo AF in HCM. METHODS: Consecutive patients with HCM underwent clinical assessment and 48-hour Holter electrocardiography to detect AF episodes. Left ventricular (LV) morphology, function and fibrosis, and the left atrium (LA) were characterized by cardiac magnetic resonance. Mitral valve, systolic pulmonary artery pressure, LV filling and maximum gradients were assessed by echocardiography. Patients with no previous history of AF were followed with Holter recordings. RESULTS: Two hundred and nine patients were included (mean age 53±16 years; 140 men), 46 (22%) of whom had a history of AF and a longer duration from HCM diagnosis, more frequent use of heart failure medication, a higher systolic pulmonary artery pressure, a lower LV ejection fraction, a higher extent of LV fibrosis and prevalence of fibrosis on right ventricular (RV)-LV insertions, a higher LA volume and lower LA phasic function. Patients with no AF at inclusion were followed for 26 (17-42) months, and 15 (9%) developed de novo AF. Among clinical characteristics, New York Heart Association class was the only significant AF predictor in the multivariable analysis (hazard ratio 2.65 per class, 95% confidence interval [CI] 1.15-6.10; P=0.02). Among imaging characteristics, two independent predictors were identified: myocardial fibrosis on RV insertions (hazard ratio 2.8, 95% CI 1.3-5.9; P=0.008); and LA volume (hazard ratio 1.03 per mL/m2, 95% CI 1.01-1.06; P=0.006). CONCLUSIONS: AF in HCM is predicted by New York Heart Association class, LA volume and LV fibrosis on RV-LV insertions on cardiac magnetic resonance imaging. The mechanisms relating the ventricular phenotype to AF should be clarified in future studies.

Social modulation of cognition: Lessons from rhesus macaques relevant to education.

Any animal, human or non-human, lives in a world where there are others like itself. Individuals' behaviors are thus inevitably influenced by others, and cognition is no exception. Long acknowledged in psychology, social modulations of cognition have been neglected in cognitive neuroscience. Yet, infusing this classic topic in psychology with brain science methodologies could yield valuable educational insights. In recent studies, we used a non-human primate model, the rhesus macaque, to identify social influences representing ancient biases rooted in evolution, and neuroimaging to shed light on underlying mechanisms. The behavioral and neural data garnered in humans and macaques are summarized, with a focus on two findings relevant to human education. First, peers' mistakes stand out as exceptional professors and seem to have devoted areas and neurons in the primates' brain. Second, peers' mere presence suffices to enhance performance in well-learned tasks, possibly by boosting activity in the brain network involved in the task at hand. These findings could be translated into concrete pedagogical interventions in the classroom.

Importance of combined left atrial size and estimated pulmonary pressure for clinical outcome in patients presenting with heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome with various phenotypes and outcomes. The prognostic relevance of echocardiography and the E/e' ratio has previously been reported. We sought to study in addition, the value of estimated pulmonary pressure and left atrial size for diagnosing and determining a prognosis for HFpEF-patients in a prospective multi-centric cohort. METHODS AND RESULTS: Patients with an acute-HF event accompanied with NT-proBNP >300 pg/mL (BNP >100 pg/mL) and LVEF >45% were included (n = 237) and clinically reassessed using echo-Doppler after 4-8 weeks of HF treatment as part of the prospective KaRen HFpEF study. A core-centre performed the echocardiographic analyses. A combined primary endpoint of either HF hospitalizations and mortality over a span of 18-month, or simply mortality (secondary endpoint) were used. The mean LVEF was 62 ± 7%, E/e':12.9 ± 6.0, left atrial volume index (LAVI): 48.1 ± 15.9 ml/m2, TR: 2.9 ± 0.9 m/s. Patients with both LAVI > 40 ml/m2 and TR > 3.1 m/s had a significantly greater risk of death or heart failure related hospitalization than others (P = 0.014 after adjustment). CONCLUSION: The combination of enlarged LA and elevated estimated pulmonary pressure has a strong prognostic impact in patients suffering from HFpEF. Our results indicate that such patients constitute a risk group in HFpEF which requires dedicated medical attention. CLINICALTRIALS.GOV: NCT00774709.

Morphological and functional abnormalities pattern in hypertrophy-free HCM mutation carriers detected with echocardiography.

To evaluate if morphological or functional abnormalities could be detected with echocardiography in hypertrophic myocardiopathy (HCM) mutation carriers without left ventricle (LV) hypertrophy has developed. HCM is caused by extensive genes mutations found in two-third of patients. Because screening for carriership of a large population is unreasonable, identification of asymptomatic subjects is confined to the use of imaging such as echocardiography, by which subtle abnormalities can be detected. Comprehensive echocardiographic studies including morphological and functional assessment were performed. Asymptomatic HCM mutation carriers without hypertrophy (Phe-/Gen+, n = 14), and HCM patients (Phe+/Gen+, n = 17) were compared with healthy control subjects (n = 32) in a prospective design. Compared to controls, septum thickness was significantly higher with an elongated mitral valve in both groups. Thickened LV muscular band (LVMB) are more likely found in Phe-/Gen+ and Phe+/Gen+. The thickness of LVMB was higher in the Phe-/Gen+ versus controls. A LVMB thickness ≥3.6 mm was associated with HCM mutation carriership (sensitivity: 76.9 %, specificity: 94.1 %). The regional strain was significantly impaired in the basal segments of the septum in the Phe-/Gen+. The GLS was significantly impaired in the Phe+/Gen+ (-16.4 % ± 2.9 vs. -21.4 % ± 2.3 in control subjects, p = 0.01). Mitral A wave velocity, septal E/e', averaged E/e' were increased in both groups. E/A ratio was significantly lower in Phe+/Gen+. Morphological and functional abnormalities in hypertrophy-free HCM mutation carriers could be detected with echocardiography. Anomalous thickened LVMB could be representing a morphological marker for the HCM disease without overt hypertrophy has developed or in patients with an ambiguous diagnosis.