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The hippocampus is a mammalian brain structure that expresses spatial representations1 and is crucial for navigation2,3. Navigation, in turn, intricately depends on locomotion; however, current accounts suggest a dissociation between hippocampal spatial representations and the details of locomotor processes. Specifically, the hippocampus is thought to represent mainly higher-order cognitive and locomotor variables such as position, speed and direction of movement4-7, whereas the limb movements that propel the animal can be computed and represented primarily in subcortical circuits, including the spinal cord, brainstem and cerebellum8-11. Whether hippocampal representations are actually decoupled from the detailed structure of locomotor processes remains unknown. To address this question, here we simultaneously monitored hippocampal spatial representations and ongoing limb movements underlying locomotion at fast timescales. We found that the forelimb stepping cycle in freely behaving rats is rhythmic and peaks at around 8 Hz during movement, matching the approximately 8 Hz modulation of hippocampal activity and spatial representations during locomotion12. We also discovered precisely timed coordination between the time at which the forelimbs touch the ground ('plant' times of the stepping cycle) and the hippocampal representation of space. Notably, plant times coincide with hippocampal representations that are closest to the actual position of the nose of the rat, whereas between these plant times, the hippocampal representation progresses towards possible future locations. This synchronization was specifically detectable when rats approached spatial decisions. Together, our results reveal a profound and dynamic coordination on a timescale of tens of milliseconds between central cognitive representations and peripheral motor processes. This coordination engages and disengages rapidly in association with cognitive demands and is well suited to support rapid information exchange between cognitive and sensory-motor circuits.

Organisms must learn new strategies to adapt to changing environments. Activity in different neurons often exhibits synchronization that can dynamically enhance their communication and might create flexible brain states that facilitate changes in behavior. We studied the role of gamma-frequency (~40 Hz) synchrony between prefrontal parvalbumin (PV) interneurons in mice learning multiple new cue-reward associations. Voltage indicators revealed cell-type-specific increases of cross-hemispheric gamma synchrony between PV interneurons when mice received feedback that previously learned associations were no longer valid. Disrupting this synchronization by delivering out-of-phase optogenetic stimulation caused mice to perseverate on outdated associations, an effect not reproduced by in-phase stimulation or out-of-phase stimulation at other frequencies. Gamma synchrony was specifically required when new associations used familiar cues that were previously irrelevant to behavioral outcomes, not when associations involved new cues or for reversing previously learned associations. Thus, gamma synchrony is indispensable for reappraising the behavioral salience of external cues.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences.

ABSTRACT Neurodata Without Borders: Neurophysiology (NWB:N) is a data standard for neurophysiology, providing neuroscientists with a common standard to share, archive, use, and build common analysis tools for neurophysiology data. With NWB:N version 2.0 (NWB:N 2.0) we made significant advances towards creating a usable standard, software ecosystem, and vibrant community for standardizing neurophysiology data. In this manuscript we focus in particular on the NWB:N data standard schema and present advances towards creating an accessible data standard for neurophysiology.

Thalamic relay neurons have well-characterized dual firing modes: bursting and tonic spiking. Studies in brain slices have led to a model in which rhythmic synchronized spiking (phasic firing) in a population of relay neurons leads to hyper-synchronous oscillatory cortico-thalamo-cortical rhythms that result in absence seizures. This model suggests that blocking thalamocortical phasic firing would treat absence seizures. However, recent in vivo studies in anesthetized animals have questioned this simple model. Here we resolve this issue by developing a real-time, mode-switching approach to drive thalamocortical neurons into or out of a phasic firing mode in two freely behaving genetic rodent models of absence epilepsy. Toggling between phasic and tonic firing in thalamocortical neurons launched and aborted absence seizures, respectively. Thus, a synchronous thalamocortical phasic firing state is required for absence seizures, and switching to tonic firing rapidly halts absences. This approach should be useful for modulating other networks that have mode-dependent behaviors.

Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC-BMA projection implements top-down control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway.

Shallow lakes and ponds undergo frequent temporary thermal stratification. How this affects greenhouse gas (GHG) emissions is moot, with both increased and reduced GHG emissions hypothesised. Here, weekly estimations of GHG emissions, over the growing season from May to September, were combined with temperature and oxygen profiles of an 11 ha temperate shallow lake to investigate how thermal stratification shapes GHG emissions. There were three main stratification periods with profound anoxia occurring in the bottom waters upon isolation from the atmosphere. Average diffusive emissions of methane (CH 4) and nitrous oxide (N 2 O) were larger and more variable in the stratified phase, whereas carbon dioxide (CO 2) was on average lower, though these differences were not statistically significant. In contrast, there was a significant order of magnitude increase in CH 4 ebullition in the stratified phase. Furthermore, at the end of the period of stratification, there was a large efflux of CH 4 and CO 2 as the lake mixed. Two relatively isolated turnover events were estimated to have released the majority of the CH 4 emitted between May and September. These results demonstrate how stratification patterns can shape GHG emissions and highlight the role of turnover emissions and the need for high-frequency measurements of GHG emissions, which are required to accurately characterise emissions, particularly from temporarily stratifying lakes. [ABSTRACT FROM AUTHOR]

Aims and objectivesThis randomised controlled trial was conducted to estimate the cost-effectiveness of a nurse-led education and psychosocial support programme for patients with heart failure (HF) and their partners.BackgroundThere are few studies evaluating cost-effectiveness of interventions among HF patient-partner dyads.MethodsDyads randomised to the experimental group received nurse-led counselling, computer-based education and written materials aimed at developing problem-solving skills at two, six and 12 weeks after hospitalisation with HF exacerbation. The dyads in the control group received usual care. A cost-effectiveness analysis that included costs associated with staff time to deliver the intervention and travel costs was conducted at 12 months. Quality-adjusted life-year (QALY) weights for patients and partners were estimated by SF-6D.ResultsA total of 155 dyads were included. The intervention cost was €223 per patient. Participants in both groups showed improvements in QALY weights after 12 months. However, no significant difference in QALY weights was found between the patients in the two groups, nor among their partners.ConclusionThe intervention was not proven cost-effective, neither for patients nor for partners. The intervention, however, had trends (but not significant) effects on the patient-partner dyads, and by analysing the QALY gained from the dyad, a reasonable mean cost-effectiveness ratio was achieved.Relevance to clinical practiceThe study shows trends of a cost-effective education and psychosocial care of HF patient-partner dyads.

Objectives: To evaluate the cost‐effectiveness of root canal treatment (RCT) compared with a tooth extraction in a general dental practice setting, with reference to cost per quality‐adjusted life‐year (QALY) gained over 1 year. Material and Methods: This is a prospective controlled cohort study based on patients either starting RCT or undergoing extraction at one of six Public Dental Service clinics in the county of Västra Götaland, Sweden. From a total of 65 patients, 2 comparable groups were formed: 37 started RCT and 28 underwent extraction. A societal perspective was used for the cost calculations. QALYs were estimated, based on the EQ‐5D‐5L given to the patients at their first treatment appointment and then after 1, 6, and 12 months. Results: The total mean cost of RCT ($689.1) was higher than for extraction ($280.1). For those patients whose extracted tooth was replaced, the costs were even higher ($1245.5). There were no significant intergroup differences in QALYs, but a significant improvement in health state values in the tooth‐preserving group. Conclusions: In the short term, extraction was cost‐effective compared with preserving a tooth with RCT. However, the potential need for future replacement of the extracted tooth, by an implant, fixed prosthesis, or removable partial dentures, may change the calculation in favor of RCT. [ABSTRACT FROM AUTHOR]