Changes in primary visual and auditory cortex of blind and sighted adults following 10 weeks of click-based echolocation training.

Recent work suggests that the adult human brain is very adaptable when it comes to sensory processing. In this context, it has also been suggested that structural "blueprints" may fundamentally constrain neuroplastic change, e.g. in response to sensory deprivation. Here, we trained 12 blind participants and 14 sighted participants in echolocation over a 10-week period, and used MRI in a pre-post design to measure functional and structural brain changes. We found that blind participants and sighted participants together showed a training-induced increase in activation in left and right V1 in response to echoes, a finding difficult to reconcile with the view that sensory cortex is strictly organized by modality. Further, blind participants and sighted participants showed a training induced increase in activation in right A1 in response to sounds per se (i.e. not echo-specific), and this was accompanied by an increase in gray matter density in right A1 in blind participants and in adjacent acoustic areas in sighted participants. The similarity in functional results between sighted participants and blind participants is consistent with the idea that reorganization may be governed by similar principles in the two groups, yet our structural analyses also showed differences between the groups suggesting that a more nuanced view may be required.

A Structure-Function Substrate of Memory for Spatial Configurations in Medial and Lateral Temporal Cortices.

Prior research has shown a role of the medial temporal lobe, particularly the hippocampal-parahippocampal complex, in spatial cognition. Here, we developed a new paradigm, the conformational shift spatial task (CSST), which examines the ability to encode and retrieve spatial relations between unrelated items. This task is short, uses symbolic cues, incorporates two difficulty levels, and can be administered inside the scanner. A cohort of 48 healthy young adults underwent the CSST, together with a set of behavioral measures and multimodal magnetic resonance imaging (MRI). Inter-individual differences in CSST performance correlated with scores on an established spatial memory paradigm, but neither with episodic memory nor mnemonic discrimination, supporting specificity. Analyzing high-resolution structural MRI data, individuals with better spatial memory showed thicker medial and lateral temporal cortices. Functional relevance of these findings was supported by task-based functional MRI analysis in the same participants and ad hoc meta-analysis. Exploratory resting-state functional MRI analyses centered on clusters of morphological effects revealed additional modulation of intrinsic network integration, particularly between lateral and medial temporal structures. Our work presents a novel spatial memory paradigm and supports an integrated structure-function substrate in the human temporal lobe. Task paradigms are programmed in python and made open access.

The Noninvasive Ventilation Outcomes (NIVO) score: prediction of in-hospital mortality in exacerbations of COPD requiring assisted ventilation.

INTRODUCTION: Acute exacerbations of COPD (AECOPD) complicated by acute (acidaemic) hypercapnic respiratory failure (AHRF) requiring ventilation are common. When applied appropriately, ventilation substantially reduces mortality. Despite this, there is evidence of poor practice and prognostic pessimism. A clinical prediction tool could improve decision making regarding ventilation, but none is routinely used. METHODS: Consecutive patients admitted with AECOPD and AHRF treated with assisted ventilation (principally noninvasive ventilation) were identified in two hospitals serving differing populations. Known and potential prognostic indices were identified a priori. A prediction tool for in-hospital death was derived using multivariable regression analysis. Prospective, external validation was performed in a temporally separate, geographically diverse 10-centre study. The trial methodology adhered to TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) recommendations. RESULTS: Derivation cohort: n=489, in-hospital mortality 25.4%; validation cohort: n=733, in-hospital mortality 20.1%. Using six simple categorised variables (extended Medical Research Council Dyspnoea score 1-4/5a/5b, time from admission to acidaemia >12 h, pH <7.25, presence of atrial fibrillation, Glasgow coma scale ≤14 and chest radiograph consolidation), a simple scoring system with strong prediction of in-hospital mortality is achieved. The resultant Noninvasive Ventilation Outcomes (NIVO) score had area under the receiver operating curve of 0.79 and offers good calibration and discrimination across stratified risk groups in its validation cohort. DISCUSSION: The NIVO score outperformed pre-specified comparator scores. It is validated in a generalisable cohort and works despite the heterogeneity inherent to both this patient group and this intervention. Potential applications include informing discussions with patients and their families, aiding treatment escalation decisions, challenging pessimism and comparing risk-adjusted outcomes across centres.

A role for the OsHKT 2;1 sodium transporter in potassium use efficiency in rice.

Increasing the potassium use efficiency (KUE) of crops is important for agricultural sustainability. However, a greater understanding of this complex trait is required to develop new, high-KUE cultivars. To this end, a genome-wide association study (GWAS) was applied to diverse rice (Oryza sativa L.) genotypes grown under potassium-stressed and -replete conditions. Using high-stringency criteria, the genetic architecture of KUE was uncovered, together with the breadth of physiological responses to low-potassium stress. Specifically, three quantitative trait loci (QTLs) were identified, which contained >90 candidate genes. Of these, the sodium transporter gene OsHKT2;1 emerged as a key factor that impacts on KUE based on (i) the correlation between shoot Na+ and KUE, and (ii) higher levels of HKT2;1 expression in high-KUE lines.

Predictors of NIV Treatment in Patients with COPD Exacerbation Complicated by Respiratory Acidaemia.

Non-invasive ventilation (NIV) treatment decisions are poorly understood for patients with COPD exacerbation complicated by acute hypercapnic respiratory failure and respiratory acidaemia (ECOPD-RA). We identified 420 NIV-eligible patients from the DECAF study cohorts admitted with an ECOPD-RA. Using bivariate and multivariate analyses, we examined which indices were associated with clinicians' decisions to start NIV, including whether the presence of pneumonia was a deterrent. Admitting hospital, admission from institutional care, partial pressure of oxygen, cerebrovascular disease, pH, systolic blood pressure and white cell count were all associated with the provision of NIV. Of these indices, only pH was also a predictor of inpatient death. Those not treated with NIV included those with milder acidaemia and higher (and sometimes excessive) oxygen levels, and a frailer population with higher Extended Medical Research Council Dyspnoea scores, presumably deemed not suitable for NIV. Pneumonia was not associated with NIV treatment; 34 of 111 (30.6%) NIV-untreated patients had pneumonia, whilst 107 of 309 (34.6%) NIV-treated patients had pneumonia (p = 0.483). In our study, one in four NIV-eligible patients were not treated with NIV. Clinicians' NIV treatment decisions are not based on those indices most strongly associated with mortality risk. One of the strongest predictors of whether a patient received a life-saving treatment is which hospital they attended. Further research is required to aid in the risk stratification of this patient group which may help standardise and improve care.

A data-driven approach to stimulus selection reveals an image-based representation of objects in high-level visual areas.

The ventral visual pathway is directly involved in the perception and recognition of objects. However, the extent to which the neural representation of objects in this region reflects low-level or high-level properties remains unresolved. A problem in resolving this issue is that only a small proportion of the objects experienced during natural viewing can be shown during a typical experiment. This can lead to an uneven sampling of objects that biases our understanding of how they are represented. To address this issue, we developed a data-driven approach to stimulus selection that involved describing a large number objects in terms of their image properties. In the first experiment, clusters of objects were evenly selected from this multi-dimensional image space. Although the clusters did not have any consistent semantic features, each elicited a distinct pattern of neural response. In the second experiment, we asked whether high-level, category-selective patterns of response could be elicited by objects from other categories, but with similar image properties. Object clusters were selected based on the similarity of their image properties to objects from five different categories (bottle, chair, face, house, and shoe). The pattern of response to each metameric object cluster was similar to the pattern elicited by objects from the corresponding category. For example, the pattern for bottles was similar to the pattern for objects with similar image properties to bottles. In both experiments, the patterns of response were consistent across participants providing evidence for common organising principles. This study provides a more ecological approach to understanding the perceptual representations of objects and reveals the importance of image properties.

Home treatment of COPD exacerbation selected by DECAF score: a non-inferiority, randomised controlled trial and economic evaluation.

BACKGROUND: Previous models of Hospital at Home (HAH) for COPD exacerbation (ECOPD) were limited by the lack of a reliable prognostic score to guide patient selection. Approximately 50% of hospitalised patients have a low mortality risk by DECAF, thus are potentially suitable. METHODS: In a non-inferiority randomised controlled trial, 118 patients admitted with a low-risk ECOPD (DECAF 0 or 1) were recruited to HAH or usual care (UC). The primary outcome was health and social costs at 90 days. RESULTS: Mean 90-day costs were £1016 lower in HAH, but the one-sided 95% CI crossed the non-inferiority limit of £150 (CI -2343 to 312). Savings were primarily due to reduced hospital bed days: HAH=1 (IQR 1-7), UC=5 (IQR 2-12) (P=0.001). Length of stay during the index admission in UC was only 3 days, which was 2 days shorter than expected. Based on quality-adjusted life years, the probability of HAH being cost-effective was 90%. There was one death within 90 days in each arm, readmission rates were similar and 90% of patients preferred HAH for subsequent ECOPD. CONCLUSION: HAH selected by low-risk DECAF score was safe, clinically effective, cost-effective, and preferred by most patients. Compared with earlier models, selection is simpler and approximately twice as many patients are eligible. The introduction of DECAF was associated with a fall in UC length of stay without adverse outcome, supporting use of DECAF to direct early discharge. TRIAL REGISTRATION NUMBER: Registered prospectively ISRCTN29082260.

Genome-wide association studies to identify rice salt-tolerance markers.

Salinity is an ever increasing menace that affects agriculture worldwide. Crops such as rice are salt sensitive, but its degree of susceptibility varies widely between cultivars pointing to extensive genetic diversity that can be exploited to identify genes and proteins that are relevant in the response of rice to salt stress. We used a diversity panel of 306 rice accessions and collected phenotypic data after short (6 h), medium (7 d) and long (30 d) salinity treatment (50 mm NaCl). A genome-wide association study (GWAS) was subsequently performed, which identified around 1200 candidate genes from many functional categories, but this was treatment period dependent. Further analysis showed the presence of cation transporters and transcription factors with a known role in salinity tolerance and those that hitherto were not known to be involved in salt stress. Localization analysis of single nucleotide polymorphisms (SNPs) showed the presence of several hundred non-synonymous SNPs (nsSNPs) in coding regions and earmarked specific genomic regions with increased numbers of nsSNPs. It points to components of the ubiquitination pathway as important sources of genetic diversity that could underpin phenotypic variation in stress tolerance.

Knowing what from where: Hippocampal connectivity with temporoparietal cortex at rest is linked to individual differences in semantic and topographic memory.

The hippocampus contributes to episodic, spatial and semantic aspects of memory, yet individual differences within and between these functions are not well-understood. In 136 healthy individuals, we investigated whether these differences reflect variation in the strength of connections between functionally-specialised segments of the hippocampus and diverse cortical regions that participate in different aspects of memory. Better topographical memory was associated with stronger connectivity between lingual gyrus and left anterior, rather than posterior, hippocampus. Better semantic memory was associated with increased connectivity between the intracalcarine/cuneus and left, rather than right, posterior hippocampus. Notably, we observed a double dissociation between semantic and topographical memory: better semantic memory was associated with stronger connectivity between left temporoparietal cortex and left anterior hippocampus, while better topographic memory was linked to stronger connectivity with right anterior hippocampus. Together these data support a division-of-labour account of hippocampal functioning: at the population level, differences in connectivity across the hippocampus reflect functional specialisation for different facets of memory, while variation in these connectivity patterns across individuals is associated with differences in the capacity to retrieve different types of information. In particular, within-hemisphere connectivity between hippocampus and left temporoparietal cortex supports conceptual processing at the expense of spatial ability.

Modeling first impressions from highly variable facial images.

First impressions of social traits, such as trustworthiness or dominance, are reliably perceived in faces, and despite their questionable validity they can have considerable real-world consequences. We sought to uncover the information driving such judgments, using an attribute-based approach. Attributes (physical facial features) were objectively measured from feature positions and colors in a database of highly variable "ambient" face photographs, and then used as input for a neural network to model factor dimensions (approachability, youthful-attractiveness, and dominance) thought to underlie social attributions. A linear model based on this approach was able to account for 58% of the variance in raters' impressions of previously unseen faces, and factor-attribute correlations could be used to rank attributes by their importance to each factor. Reversing this process, neural networks were then used to predict facial attributes and corresponding image properties from specific combinations of factor scores. In this way, the factors driving social trait impressions could be visualized as a series of computer-generated cartoon face-like images, depicting how attributes change along each dimension. This study shows that despite enormous variation in ambient images of faces, a substantial proportion of the variance in first impressions can be accounted for through linear changes in objectively defined features.

Patterns of neural response in scene-selective regions of the human brain are affected by low-level manipulations of spatial frequency.

Neuroimaging studies have found distinct patterns of response to different categories of scenes. However, the relative importance of low-level image properties in generating these response patterns is not fully understood. To address this issue, we directly manipulated the low level properties of scenes in a way that preserved the ability to perceive the category. We then measured the effect of these manipulations on category-selective patterns of fMRI response in the PPA, RSC and OPA. In Experiment 1, a horizontal-pass or vertical-pass orientation filter was applied to images of indoor and natural scenes. The image filter did not have a large effect on the patterns of response. For example, vertical- and horizontal-pass filtered indoor images generated similar patterns of response. Similarly, vertical- and horizontal-pass filtered natural scenes generated similar patterns of response. In Experiment 2, low-pass or high-pass spatial frequency filters were applied to the images. We found that image filter had a marked effect on the patterns of response in scene-selective regions. For example, low-pass indoor images generated similar patterns of response to low-pass natural images. The effect of filter varied across different scene-selective regions, suggesting differences in the way that scenes are represented in these regions. These results indicate that patterns of response in scene-selective regions are sensitive to the low-level properties of the image, particularly the spatial frequency content.

Effects of rhythm on memory for spoken sequences: A model and tests of its stimulus-driven mechanism.

Immediate memory for spoken sequences depends on their rhythm - different levels of accuracy and patterns of error are seen according to the way in which items are spaced in time. Current models address these phenomena only partially or not at all. We investigate the idea that temporal grouping effects are an emergent property of a general serial ordering mechanism based on a population of oscillators locally-sensitive to amplitude modulations on different temporal scales. Two experiments show that the effects of temporal grouping are independent of the predictability of the grouping pattern, consistent with this model's stimulus-driven mechanism and inconsistent with alternative accounts in terms of top-down processes. The second experiment reports detailed and systematic differences in the recall of irregularly grouped sequences that are broadly consistent with predictions of the new model. We suggest that the bottom-up multi-scale population oscillator (or BUMP) mechanism is a useful starting point for a general account of serial order in language processing more widely.

Low-level image properties of visual objects predict patterns of neural response across category-selective regions of the ventral visual pathway.

Neuroimaging studies have revealed strong selectivity for object categories in high-level regions of the human visual system. However, it is unknown whether this selectivity is truly based on object category, or whether it reflects tuning for low-level features that are common to images from a particular category. To address this issue, we measured the neural response to different object categories across the ventral visual pathway. Each object category elicited a distinct neural pattern of response. Next, we compared the patterns of neural response between object categories. We found a strong positive correlation between the neural patterns and the underlying low-level image properties. Importantly, this correlation was still evident when the within-category correlations were removed from the analysis. Next, we asked whether basic image properties could also explain variation in the pattern of response to different exemplars from one object category (faces). A significant correlation was also evident between the similarity of neural patterns of response and the low-level properties of different faces, particularly in regions associated with face processing. These results suggest that the appearance of category-selective regions at this coarse scale of representation may be explained by the systematic convergence of responses to low-level features that are characteristic of each category.

Low-level properties of natural images predict topographic patterns of neural response in the ventral visual pathway.

Neuroimaging research over the past 20 years has begun to reveal a picture of how the human visual system is organized. A key distinction that has arisen from these studies is the difference in the organization of low-level and high-level visual regions. Low-level regions contain topographic maps that are tightly linked to properties of the image. In contrast, high-level visual areas are thought to be arranged in modules that are tightly linked to categorical or semantic information in the image. To date, an unresolved question has been how the strong functional selectivity for object categories in high-level visual regions might arise from the image-based representations found in low-level visual regions. Here, we review recent evidence suggesting that patterns of response in high-level visual areas may be better explained by response to image properties that are characteristic of different object categories.

Patterns of response to visual scenes are linked to the low-level properties of the image.

Scene-selective regions in the brain play an important role in the way that we navigate through our visual environment. However, the principles that govern the organization of these regions are not fully understood. For example, it is not clear whether patterns of response in scene-selective regions are linked to high-level semantic category or to low-level spatial structure in scenes. To address this issue, we used multivariate pattern analysis with fMRI to compare patterns of response to different categories of scenes. Although we found distinct patterns of neural response to each category of scene, the magnitude of the within-category similarity varied across different scenes. To determine whether this variation in the categorical response to scenes could reflect variation in the low-level image properties, we measured the similarity of images from each category of scene. Although we found that the low-level properties of images from each category were more similar to each other than to other categories of scenes, we also found that the magnitude of the within-category similarity varied across different scenes. Finally, we compared variation in the neural response to different categories of scenes with corresponding variation in the low-level image properties. We found a strong positive correlation between the similarity in the patterns of neural response to different scenes and the similarity in the image properties. Together, these results suggest that categorical patterns of response to scenes are linked to the low-level properties of the images.

Anterior hippocampus and goal-directed spatial decision making.

Planning spatial paths through our environment is an important part of everyday life and is supported by a neural system including the hippocampus and prefrontal cortex. Here we investigated the precise functional roles of the components of this system in humans by using fMRI as participants performed a simple goal-directed route-planning task. Participants had to choose the shorter of two routes to a goal in a visual scene that might contain a barrier blocking the most direct route, requiring a detour, or might be obscured by a curtain, requiring memory for the scene. The participant's start position was varied to parametrically manipulate their proximity to the goal and the difference in length of the two routes. Activity in medial prefrontal cortex, precuneus, and left posterior parietal cortex was associated with detour planning, regardless of difficulty, whereas activity in parahippocampal gyrus was associated with remembering the spatial layout of the visual scene. Activity in bilateral anterior hippocampal formation showed a strong increase the closer the start position was to the goal, together with medial prefrontal, medial and posterior parietal cortices. Our results are consistent with computational models in which goal proximity is used to guide subsequent navigation and with the association of anterior hippocampal areas with nonspatial functions such as arousal and reward expectancy. They illustrate how spatial and nonspatial functions combine within the anterior hippocampus, and how these functions interact with parahippocampal, parietal, and prefrontal areas in decision making and mnemonic function.

Screening success: A virtual MDT can reduce the number of patients requiring respiratory follow-up post-COVID-19 pneumonia in line with British Thoracic Society guidance.

Introduction and objectivesThe ongoing respiratory sequelae of COVID-19 pneumonia remain unclear, and the ideal follow-up of these patients is still a work in progress. We describe our experience of using a pre-follow-up multidisciplinary team (MDT) to decide the follow-up stream in patients hospitalised for COVID-19 pneumonia. METHODS: We reviewed all patients with a clinico-radiological diagnosis of COVID-19 admitted to hospital during a 3-month period and assigned a follow-up stream based on British Thoracic Society guidance. RESULTS: We changed the follow-up pathway in 71% (277/392) and refined the pathway in 67% (261/392) of indeterminate cases. We also created an automated process for the general practitioner to book follow-up imaging and will use this process going forward. CONCLUSION: These findings highlight the importance of the MDT review of cases with suspected COVID-19 pneumonia prior to clinic attendance to ensure appropriate patients are followed up and to optimise utilisation of outpatient imaging and clinics.

Selectivity for low-level features of objects in the human ventral stream.

Category selective regions in the ventral visual stream are considered to support higher-level representations of objects. The aim of this study was to determine the extent to which category selectivity in face and place regions can be explained by selectivity for low-level features of these complex objects. First, we compared the relative responses to intact and Fourier-scrambled images of faces and places. Next, we compared the magnitude of fMR adaptation to both intact and scrambled faces and places. The results revealed that global differences in the amplitude spectrum of face and place images can explain a small proportion of the category selectivity that is found in regions such as the fusiform face area (FFA) and parahippocampal place area (PPA). However, a whole-brain analysis revealed selectivity to scrambled images in more posterior regions of the ventral stream. Consistent with the pattern evident for intact images, more lateral regions responded selectively to scrambled faces, whereas more medial regions responded more strongly to scrambled places. These findings suggest that selectivity for object categories emerges from the differential processing of low-level features that are typical of different object categories in early visual areas.

Topographical short-term memory differentiates Alzheimer's disease from frontotemporal lobar degeneration.

We used a recently developed test of spatial memory--the Four Mountains Test--to investigate the core cognitive processes underpinning topographical disorientation in patients with amnestic mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD). Performance of these clinical groups was compared with age-matched controls, patients with frontotemporal lobar degeneration (FTLD), and patients with subjective memory impairments. We investigated the perception (concurrent match-to-sample) and short-term retention (2-s delayed match-to-sample) of the configuration of topographical features in computer-generated landscapes shown from different viewpoints. Thirty-one patients were tested (7 AD, 6 a-MCI, 7 temporal variant FTLD, 5 frontal variant FTLD, 6 subjective memory impairment) and 25 age- and gender-matched controls. Brain MRI was available for 27 patients; medial temporal lobe atrophy was assessed using a visual rating scale. Patients with a-MCI or mild AD were impaired on topographical short-term memory, but not perception. No other group differences were found on the topographical subtests. Notably, patients with temporal variants of FTLD performed normally, regardless of the laterality of damage. Subtests for the perception and retention of nonspatial aspects of the landscapes (weather conditions, seasonal and daily variations in lighting and color) were poor at differentiating the patient groups. These results indicate a core deficit in representing topographical layout, even for very short durations, within the context of more general long-term memory impairments found in AD, and suggest that this function is particularly sensitive to the earliest stages of the disease.

Effect of portable non-invasive ventilation on exercise tolerance in COPD: One size does not fit all.

In a cross-over RCT, portable NIV (pNIV) reduced dynamic hyperinflation (DH) compared to pursed lip breathing (PLB) during recovery from intermittent exercise in COPD, but not consistently in all subjects. In this post-hoc analysis, DH response was defined as a reduction ≥4.5 % of predicted resting inspiratory capacity with pNIV compared to PLB. At exercise iso-time (where work completed was consistent between pNIV and PLB), 8/24 patients were DH non-responders (DH: 240 ± 40 mL, p = 0.001 greater using pNIV). 16/24 were DH responders (DH: 220 ± 50 mL, p = 0.001 lower using pNIV). Compared to DH responders, DH non-responders exhibited greater resting DH (RV/TLC: 65 ± 4% versus 56 ± 2%; p = 0.028) and did not improve exercise tolerance (pNIV: 30.9 ± 3.4 versus PLB: 29.9 ± 3.3 min; p = 0.603). DH responders increased exercise tolerance (pNIV: 34.9 ± 2.4 versus PLB: 27.1 ± 2.3 min; p = 0.001). Resting RV/TLC% was negatively associated with the magnitude of DH when using pNIV compared to PLB (r=-0.42; p = 0.043). Patients with profound DH were less likely to improve exercise tolerance with pNIV. Further studies using auto-adjusted ventilators are warranted.