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A growing body of literature demonstrates strong effects of ovarian hormones on the hippocampus and adjacent structures. However, resulting impacts on human cognition remain unclear. Addressing this gap, we examine pattern separation ability, a core hippocampal process, across the menstrual cycle using the mnemonic similarity task as a behavioral index (N = 183). We find a non-linear effect of the menstrual cycle, with pattern separation performance peaking in the high-estradiol, late follicular phase and reaching its lowest point during the mid-luteal phase, which is characterized by moderate estradiol and high progesterone levels. Additionally, we find that perceived stress may facilitate pattern separation performance. These results point to the importance of ovarian hormones for human cognition, reveal novel effects of perceived stress on mnemonic similarity task performance, and provide preliminary evidence of possible effects of menstrual cycle phase on neural pathways involved in pattern separation.

Prefrontal cortex (PFC) is thought to support the ability to focus on goal-relevant information by filtering out irrelevant information, a process akin to dimensionality reduction. Here, we test this dimensionality reduction hypothesis by relating a data-driven approach to characterizing the complexity of neural representation with a theoretically-supported computational model of learning. We find evidence of goal-directed dimensionality reduction within human ventromedial PFC during learning. Importantly, by using computational predictions of each participant’s attentional strategies during learning, we find that that the degree of neural compression predicts an individual’s ability to selectively attend to concept-specific information. These findings suggest a domain-general mechanism of learning through compression in ventromedial PFC. Efficient learning is akin to goal-directed dimensionality reduction, in which relevant information is highlighted and irrelevant input is ignored. Here, the authors show that ventromedial prefrontal cortex uniquely supports such learning by compressing neural codes to represent goal-specific information.

A previous analysis in this trial showed that among patients with severe, symptomatic aortic stenosis who were at low surgical risk, the rate of the composite end point of death, stroke, or rehospitalization at 1 year was significantly lower with transcatheter aortic-valve replacement (TAVR) than with surgical aortic-valve replacement. Longer-term outcomes are unknown. We randomly assigned patients with severe, symptomatic aortic stenosis and low surgical risk to undergo either TAVR or surgery. The first primary end point was a composite of death, stroke, or rehospitalization related to the valve, the procedure, or heart failure. The second primary end point was a hierarchical composite that included death, disabling stroke, nondisabling stroke, and the number of rehospitalization days, analyzed with the use of a win ratio analysis. Clinical, echocardiographic, and health-status outcomes were assessed through 5 years. A total of 1000 patients underwent randomization: 503 patients were assigned to undergo TAVR, and 497 to undergo surgery. A component of the first primary end point occurred in 111 of 496 patients in the TAVR group and in 117 of 454 patients in the surgery group (Kaplan-Meier estimates, 22.8% in the TAVR group and 27.2% in the surgery group; difference, -4.3 percentage points; 95% confidence interval [CI], -9.9 to 1.3; P = 0.07). The win ratio for the second primary end point was 1.17 (95% CI, 0.90 to 1.51; P = 0.25). The Kaplan-Meier estimates for the components of the first primary end point were as follows: death, 10.0% in the TAVR group and 8.2% in the surgery group; stroke, 5.8% and 6.4%, respectively; and rehospitalization, 13.7% and 17.4%. The hemodynamic performance of the valve, assessed according to the mean (±SD) valve gradient, was 12.8±6.5 mm Hg in the TAVR group and 11.7±5.6 mm Hg in the surgery group. Bioprosthetic-valve failure occurred in 3.3% of the patients in the TAVR group and in 3.8% of those in the surgery group. Among low-risk patients with severe, symptomatic aortic stenosis who underwent TAVR or surgery, there was no significant between-group difference in the two primary composite outcomes. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.).

Transcatheter repair of secondary mitral regurgitation was associated with a lower rate of hospitalization for heart failure and lower all-cause mortality than medical therapy at 5 years of follow-up.

Concepts organize the relationship among individual stimuli or events by highlighting shared features. Often, new goals require updating conceptual knowledge to reflect relationships based on different goal-relevant features. Here, our aim is to determine how hippocampal (HPC) object representations are organized and updated to reflect changing conceptual knowledge. Participants learned two classification tasks in which successful learning required attention to different stimulus features, thus providing a means to index how representations of individual stimuli are reorganized according to changing task goals. We used a computational learning model to capture how people attended to goal-relevant features and organized object representations based on those features during learning. Using representational similarity analyses of functional magnetic resonance imaging data, we demonstrate that neural representations in left anterior HPC correspond with model predictions of concept organization. Moreover, we show that during early learning, when concept updating is most consequential, HPC is functionally coupled with prefrontal regions. Based on these findings, we propose that when task goals change, object representations in HPC can be organized in new ways, resulting in updated concepts that highlight the features most critical to the new goal.

The hippocampus is a key structure in cognition. Although much research has focused on defining the functions of its anatomically distinct subfields, the communication among these subfields within the hippocampal circuit, supported by white matter pathways, is theoretically key to emergent cognitive function. Yet, hippocampal white matter connections in humans have not been fully explored in vivo. By leveraging diffusion‐weighted imaging and a large healthy sample (N = 653), we developed a processing pipeline for in vivo quantification of human hippocampal pathways. We provided evidence for monosynaptic and trisynaptic pathway‐related connections in humans, supporting the described hippocampal circuit in ex vivo and animal studies. In addition to hemispheric and sex differences, the individual variability in hippocampal pathways was linked to cognitive abilities. Thus, in vivo characterization of human hippocampal pathways highlights the individual differences within these structures and paves the way for their implications in cognition, aging, and diseases. By leveraging diffusion‐weighted imaging and a large healthy sample (N = 653), we developed a processing pipeline for in vivo quantification of human hippocampal pathways. We provided evidence for hippocampal pathway‐related connections in humans, supporting the described hippocampal circuit in ex vivo and animal studies.

Real-world categories often contain exceptions that disobey the perceptual regularities followed by other members. Prominent psychological and neurobiological theories indicate that exception learning relies on the flexible modulation of object representations, but the specific representational shifts key to learning remain poorly understood. Here, we leveraged behavioral and computational approaches to elucidate the representational dynamics during the acquisition of exceptions that violate established regularity knowledge. In our study, participants ( n = 42) learned novel categories in which regular and exceptional items were introduced successively; we then fitted a computational model to individuals’ categorization performance to infer latent stimulus representations before and after exception learning. We found that in the representational space, exception learning not only drove confusable exceptions to be differentiated from regular items, but also led exceptions within the same category to be integrated based on shared characteristics. These shifts resulted in distinct representational clusters of regular items and exceptions that constituted hierarchically structured category representations, and the distinct clustering of exceptions from regular items was associated with a high ability to generalize and reconcile knowledge of regularities and exceptions. Moreover, by having a second group of participants ( n = 42) to judge stimuli’s similarity before and after exception learning, we revealed misalignment between representational similarity and behavioral similarity judgments, which further highlights the hierarchical layouts of categories with regularities and exceptions. Altogether, our findings elucidate the representational dynamics giving rise to generalizable category structures that reconcile perceptually inconsistent category members, thereby advancing the understanding of knowledge formation.

The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that mortality at 1 year, 2 years, and 3 years is much the same with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) for high-risk patients with aortic stenosis. We report here the 5-year outcomes. We did this randomised controlled trial at 25 hospitals, in Canada (two), Germany (one), and the USA (23). We used a computer-generated randomisation sequence to randomly assign high-risk patients with severe aortic stenosis to either SAVR or TAVR with a balloon-expandable bovine pericardial tissue valve by either a transfemoral or transapical approach. Patients and their treating physicians were not masked to treatment allocation. The primary outcome of the trial was all-cause mortality in the intention-to-treat population at 1 year, we present here predefined outcomes at 5 years. The study is registered with ClinicalTrials.gov, number NCT00530894. We screened 3105 patients, of whom 699 were enrolled (348 assigned to TAVR, 351 assigned to SAVR). Overall mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 11·7%. At 5 years, risk of death was 67·8% in the TAVR group compared with 62·4% in the SAVR group (hazard ratio 1·04, 95% CI 0·86–1·24; p=0·76). We recorded no structural valve deterioration requiring surgical valve replacement in either group. Moderate or severe aortic regurgitation occurred in 40 (14%) of 280 patients in the TAVR group and two (1%) of 228 in the SAVR group (p<0·0001), and was associated with increased 5-year risk of mortality in the TAVR group (72·4% for moderate or severe aortic regurgitation vs 56·6% for those with mild aortic regurgitation or less; p=0·003). Our findings show that TAVR as an alternative to surgery for patients with high surgical risk results in similar clinical outcomes. Edwards Lifesciences.

Secondary mitral regurgitation, which results from left ventricular dysfunction or remodeling or atrial disease, is associated with adverse cardiovascular outcomes. Treatment includes guideline-directed medical therapy for heart failure, if present, and in some cases, surgery or transcatheter intervention.

The field of mitral valve disease diagnosis and management is rapidly changing. New understanding of disease pathology and progression, with improvements in and increased use of sophisticated imaging modalities, have led to early diagnosis and complex treatment. In primary mitral regurgitation, surgical repair is the standard of care. Treatment of asymptomatic patients with severe mitral regurgitation in valve reference centres, in which successful repair is more than 95% and surgical mortality is less than 1%, should be the expectation for the next 5 years. Transcatheter mitral valve repair with a MitraClip device is also producing good outcomes in patients with primary mitral regurgitation who are at high surgical risk. Findings from clinical trials of MitraClip versus surgery in patients of intermediate surgical risk are expected to be initiated in the next few years. In patients with secondary mitral regurgitation, mainly a disease of the left ventricle, the vision for the next 5 years is not nearly as clear. Outcomes from ongoing clinical trials will greatly inform this field. Use of transcatheter techniques, both repair and replacement, is expected to substantially expand. Mitral annular calcification is an increasing problem in elderly people, causing both mitral stenosis and regurgitation which are difficult to treat. There is anecdotal experience with use of transcatheter valves by either a catheter-based approach or as a hybrid technique with open surgery, which is being studied in early feasibility trials.