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Subcortical T2-weighted (T2w) lesions are very common in older adults and have been associated with dementia. However, little is known about the strategic lesion distribution and how lesion patterns relate to vascular risk factors and cognitive impairment. The aim of this study was to analyze the association between T2w lesion load and location, vascular risk factors, and cognitive impairment in a large cohort of older adults. 1017 patients participating in a large prospective cohort study (INtervention project on cerebroVAscular disease and Dementia in the district of Ebersberg, INVADE II) were analyzed. Cerebral T2w white matter and deep grey matter lesions, the so-called white matter hyperintensities (WMHs), were outlined semi-automatically on fluid attenuated inversion recovery images and normalized to standard stereotaxic space (MNI152) by non-linear registration. Patients were assigned to either a low-risk or a high-risk group. The risk assessment considered ankle brachial index, intima media thickness, carotid artery stenosis, atrial fibrillation, previous cerebro-/cardiovascular events and peripheral artery disease as well as a score based on cholesterol levels, blood pressure and smoking. Separate lesion distributions were obtained for the two risk groups and compared using voxel-based lesion-symptom mapping. Moreover, we assessed the relation between lesion location and cognitive impairment (demographically adjusted z-scores of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery Plus, CERAD-NAB Plus) using voxel-based statistics (α = 0.05). A total of 878 out of 1017 subjects (86%) had evaluable MRI data and were included in the analyses (mean age: 68.2 ± 7.6 years, female: 515). Patients in the high-risk group were characterized by a significantly higher age, a higher proportion of men, a higher lesion load (p < 0.001), and a worse performance in some of the cognitive subdomain scores (p < 0.05). Voxels with significant associations to the subjects' cerebrovascular risk profiles were mainly found at locations of the corpus callosum, superior corona radiata, superior longitudinal fasciculus, internal and external capsule, and putamen. While several cognitive domains have shown significant associations with the participants’ total lesion burden (p < 0.05), no focal WMH locations were found to be associated with cognitive impairment. Age, gender, several cognitive scores, and WMH lesion load were shown to be significantly associated with vascular risk factors in a population of older, but cognitively preserved adults. Vascular risk factors seem to promote lesion formation most severely at well-defined locations. While lesion load showed weak associations to some cognitive scores, no focal locations causing specific cognitive disturbances were identified in this large cohort of older adults. •Study of association between T2w lesion load and location, vascular risk factors, cognition.•Increased vascular risk reflected in higher age, proportion of men, lesion load, cognitive disturbances.•Periventricular lesions significantly associated with vascular risk factors.•Total lesion burden but not focal locations partially explain cognitive disturbances.

White matter hyperintensities (WMH) are a frequent finding on brain MRI of elderly subjects, and have been associated with various risk factors, as well as with development of cognitive and functional impairment. While an overall association between WMH load and risk factors is well described, possible spatially restricted vulnerability remains to be established. The aim of this study was to investigate the spatial distribution of WMH in normally functioning elderly subjects. We introduce a voxel-based approach in which lesion probability is mapped as a function of clinical risk factors using logistic regression, and validate the method using simulated datasets. The method was then applied in a total of 605 participants of the LADIS study (age 74±5years, all with WMH), and the location of manually delineated WMH was investigated after spatial normalisation. Particularly strong and widespread associations were found for age, gender and hypertension. Different distribution patterns were found for men and women. Further, increased probability was found in association with self-reported alcohol and tobacco consumption, as well as in those with a history of migraine. It is concluded that the location of WMH is dependent on the risk factors involved pointing towards a regionally different pathogenesis and/or vulnerability of the white matter. ► White matter changes are a frequent finding on brain MRI of elderly subjects. ► Overall severity is known to be associated with vascular risk factors. ► The spatial distribution of risk factor impact not well described. ► We apply voxel-based logistic regression to a large group of non-demented elderly. ► Particularly strong associations were found for age, gender and hypertension.

Much is known about how people make decisions under varying levels of probability (risk). Less is known about the neural basis of decision-making when probabilities are uncertain because of missing information (ambiguity). In decision theory, ambiguity about probabilities should not affect choices. Using functional brain imaging, we show that the level of ambiguity in choices correlates positively with activation in the amygdala and orbitofrontal cortex, and negatively with a striatal system. Moreover, striatal activity correlates positively with expected reward. Neurological subjects with orbitofrontal lesions were insensitive to the level of ambiguity and risk in behavioral choices. These data suggest a general neural circuit responding to degrees of uncertainty, contrary to decision theory.

Background To develop a regression neural network for the reconstruction of lesion probability maps on Magnetic Resonance Fingerprinting using echo-planar imaging (MRF-EPI) in addition to T 1 , T 2 ∗ , NAWM, and GM- probability maps. Methods We performed MRF-EPI measurements in 42 patients with multiple sclerosis and 6 healthy volunteers along two sites. A U-net was trained to reconstruct the denoised and distortion corrected T 1 and T 2 ∗ maps, and to additionally generate NAWM-, GM-, and WM lesion probability maps. Results WM lesions were predicted with a dice coefficient of 0.61 ± 0.09 and a lesion detection rate of 0.85 ± 0.25 for a threshold of 33%. The network jointly enabled accurate T 1 and T 2 ∗ times with relative deviations of 5.2% and 5.1% and average dice coefficients of 0.92 ± 0.04 and 0.91 ± 0.03 for NAWM and GM after binarizing with a threshold of 80%. Conclusion DL is a promising tool for the prediction of lesion probability maps in a fraction of time. These might be of clinical interest for the WM lesion analysis in MS patients.

Background Onchocerciasis is a neglected tropical filarial disease transmitted by the bites of blackflies, causing blindness and severe skin lesions. The change in focus for onchocerciasis management from control to elimination requires thorough mapping of pre-control endemicity to identify areas requiring interventions and to monitor progress. Onchocerca volvulus nodule prevalence in sub-Saharan Africa is spatially continuous and heterogeneous, and highly endemic areas may contribute to transmission in areas of low endemicity or vice-versa. Ethiopia is one such onchocerciasis-endemic country with heterogeneous O. volvulus nodule prevalence, and many districts are still unmapped despite their potential for onchocerciasis transmission. Methodology/Principle findings A Bayesian geostatistical model was fitted for retrospective pre-intervention nodule prevalence data collected from 916 unique sites and 35,077 people across Ethiopia. We used multiple environmental, socio-demographic, and climate variables to estimate the pre-intervention prevalence of O. volvulus nodules across Ethiopia and to explore their relationship with prevalence. Prevalence was high in southern and northwestern Ethiopia and low in Ethiopia's central and eastern parts. Distance to the nearest river (RR: 0.9850, 95% BCI: 0.9751-0.995), precipitation seasonality (RR: 0.9837, 95% BCI: 0.9681-0.9995), and flow accumulation (RR: 0.9586, 95% BCI: 0.9321-0.9816) were negatively associated with O. volvulus nodule prevalence, while soil moisture (RR: 1.0218, 95% BCI: 1.0135-1.0302) was positively associated. The model estimated the number of pre-intervention cases of O. volvulus nodules in Ethiopia to be around 6.48 million (95% BCI: 3.53-13.04 million). Conclusions/Significance Nodule prevalence distribution was correlated with habitat suitability for vector breeding and associated biting behavior. The modeled pre-intervention prevalence can be used as a guide for determining priorities for elimination mapping in regions of Ethiopia that are currently unmapped, most of which have comparatively low infection prevalence.

White matter hyperintensities (WMH), also known as white matter lesions, are localised white matter areas that appear hyperintense on MRI scans. WMH commonly occur in the ageing population, and are often associated with several factors such as cognitive disorders, cardiovascular risk factors, cerebrovascular and neurodegenerative diseases. Despite the fact that some links between lesion location and parametric factors such as age have already been established, the relationship between voxel-wise spatial distribution of lesions and these factors is not yet well understood. Hence, it would be of clinical importance to model the distribution of lesions at the population-level and quantitatively analyse the effect of various factors on the lesion distribution model. In this work we compare various methods, including our proposed method, to generate voxel-wise distributions of WMH within a population with respect to various factors. Our proposed Bayesian spline method models the spatio-temporal distribution of WMH with respect to a parametric factor of interest, in this case age, within a population. Our probabilistic model takes as input the lesion segmentation binary maps of subjects belonging to various age groups and provides a population-level parametric lesion probability map as output. We used a spline representation to ensure a degree of smoothness in space and the dimension associated with the parameter, and formulated our model using a Bayesian framework. We tested our algorithm output on simulated data and compared our results with those obtained using various existing methods with different levels of algorithmic and computational complexity. We then compared the better performing methods on a real dataset, consisting of 1000 subjects of the UK Biobank, divided in two groups based on hypertension diagnosis. Finally, we applied our method on a clinical dataset of patients with vascular disease. On simulated dataset, the results from our algorithm showed a mean square error (MSE) value of 7.27×10−5, which was lower than the MSE value reported in the literature, with the advantage of being robust and computationally efficient. In the UK Biobank data, we found that the lesion probabilities are higher for the hypertension group compared to the non-hypertension group and further verified this finding using a statistical t-test. Finally, when applying our method on patients with vascular disease, we observed that the overall probability of lesions is significantly higher in later age groups, which is in line with the current literature.

Root‐lesion nematodes (RLN) pose a significant threat to chickpea (Cicer arietinum L.) by damaging the root system and causing up to 25% economic losses due to reduced yield. Worldwide commercially grown chickpea varieties lack significant genetic resistance to RLN, necessitating the identification of genetic variants contributing to natural resistance. This study identifies genomic loci responsible for resistance to the RLN, Pratylenchus thornei Sher & Allen, in chickpea by utilizing high‐quality single nucleotide polymorphisms from whole‐genome sequencing data of 202 chickpea accessions. Phenotypic evaluations of the genetically diverse set of chickpea accessions in India and Australia revealed a wide range of responses from resistant to susceptible. Genome‐wide association studies (GWAS) employing Fixed and Random Model Circulating Probability Unification (FarmCPU) and Bayesian‐Information and Linkage‐Disequilibrium Iteratively Nested Keyway (BLINK) models identified 44 marker‐trait associations distributed across all chromosomes except Ca1. Crucially, genomic regions on Ca2 and Ca5 consistently display significant associations across locations. Of 25 candidate genes identified, five genes were putatively involved in RLN resistance response (glucose‐6‐phosphate dehydrogenase, heat shock proteins, MYB‐like DNA‐binding protein, zinc finger FYVE protein and pathogenesis‐related thaumatin‐like protein). One notably identified gene (Ca_10016) presents four haplotypes, where haplotypes 1–3 confer moderate susceptibility, and haplotype 4 contributes to high susceptibility to RLN. This information provides potential targets for marker development to enhance breeding for RLN resistance in chickpea. Additionally, five potential resistant genotypes (ICC3512, ICC8855, ICC5337, ICC8950, and ICC6537) to P. thornei were identified based on their performance at a specific location. The study's significance lies in its comprehensive approach, integrating multiple‐location phenotypic evaluations, advanced GWAS models, and functional genomics to unravel the genetic basis of P. thornei resistance. The identified genomic regions, candidate genes, and haplotypes offer valuable insights for breeding strategies, paving the way for developing chickpea varieties resilient to P. thornei attack. Core Ideas Five accessions (ICC3512, ICC8855, ICC5337, ICC8950, and ICC6537) emerged as resistant to root‐lesion nematodes. Forty‐four marker‐trait associations for RLN resistance were identified. Genes like glucose‐6‐phosphate dehydrogenase (G6PDH), heat shock proteins (HSPs), MYB‐like DNA‐binding protein, zinc finger FYVE protein, and PR‐related thaumatin‐like proteins are associated with RLN resistance. Haplotype analysis of candidate genes, particularly Ca_10016, revealed associations with RLN susceptibility, providing insights for further breeding efforts. Plain Language Summary Chickpeas are vital crops for India and Australia but face threats from root‐lesion nematodes (RLN), which cause significant yield losses. We aim to identify new sources of resistance and understand its genetic basis. Significant variations in RLN reproduction were observed in the chickpea diversity panel. Promising genotypes, including ICC3512, ICC8855, ICC5337, ICC8950, and ICC6537 were identified for further genetic investigation. Association studies revealed 44 genetic markers associated with RLN responses. Functional analysis identified 24 genes involved in plant‐nematode responses, including G6PDH, heat shock proteins (HSPs), MYB‐like DNA‐binding protein, zinc finger FYVE protein, and thaumatin‐like proteins. Notably, gene Ca_10016 displayed four variations, three conferring moderate susceptibility and one conferring high susceptibility. These findings offer opportunities for marker development, accelerating breeding efforts for RLN‐resistant varieties, ensuring stable production, and enhancing food security in both nations.

A somewhat perplexing finding in the systems neuroscience has been the observation that physical injury to neural systems may result in enhanced functional connectivity (i.e., hyperconnectivity) relative to the typical network response. The consequences of local or global enhancement of functional connectivity remain uncertain and this is particularly true for the overall metabolic cost of the network. We examine the hyperconnectivity hypothesis in a sample of 14 individuals with TBI with data collected at approximately 3, 6, and 12 months following moderate and severe TBI. As anticipated, individuals with TBI showed increased network strength and cost early after injury, but by one-year post injury hyperconnectivity was more circumscribed to frontal DMN and temporal-parietal attentional control regions. Cost in these subregions was a significant predictor of cognitive performance. Cost-efficiency analysis in the Power 264 data parcellation suggested that at 6 months post injury the network requires higher cost connections to achieve high efficiency as compared to the network 12 months post injury. These results demonstrate that networks self-organize to re-establish connectivity while balancing cost-efficiency trade-offs.

Recent diffusion MRI studies of stroke in humans and animals have shown that the quantitative parameters characterising the degree of non-Gaussianity of the diffusion process are much more sensitive to ischemic changes than the apparent diffusion coefficient (ADC) considered so far as the \"gold standard\". The observed changes exceeded that of the ADC by a remarkable factor of 2 to 3. These studies were based on the novel non-Gaussian methods, such as diffusion kurtosis imaging (DKI) and log-normal distribution function imaging (LNDFI). As shown in our previous work investigating the animal stroke model, a combined analysis using two methods, DKI and LNDFI provides valuable complimentary information. In the present work, we report the application of three non-Gaussian diffusion models to quantify the deviations from the Gaussian behaviour in stroke induced by transient middle cerebral artery occlusion in rat brains: the gamma-distribution function (GDF), the stretched exponential model (SEM), and the biexponential model. The main goal was to compare the sensitivity of various non-Gaussian metrics to ischemic changes and to investigate if a combined application of several models will provide added value in the assessment of stroke. We have shown that two models, GDF and SEM, exhibit a better performance than the conventional method and allow for a significantly enhanced visualization of lesions. Furthermore, we showed that valuable information regarding spatial properties of stroke lesions can be obtained. In particular, we observed a stratified cortex structure in the lesions that were well visible in the maps of the GDF and SEM metrics, but poorly distinguishable in the ADC-maps. Our results provided evidence that cortical layers tend to be differently affected by ischemic processes.

Neurons in the mature visual cortex deprived of their normal retinotopic inputs by matched binocular retinal lesions are initially silenced but become reactivated with time when the \"blind\" cortical lesion projection zone (LPZ) is filled in by new suprathreshold visual responses. In an attempt to gain further insight into the dynamics of this process, we investigated in detail the spatiotemporal pattern of single-cell properties and recording probability during cortical reorganization up to 12 months after retinal lesions. In the early phases of filling in, a transient peak of hyperactivity moves from the border of the normal cortex into the LPZ and forms the leading edge of a functional reconnection process. In the course of this process hyperactive cells inside the LPZ develop ectopic receptive fields that are initially enlarged and regain orientation specificity. During the proceeding recovery, hyperactivity and receptive field size normalize, while the quality of orientation tuning remains reduced at longer distances inside the LPZ at all stages of recovery up to 1 year. Within the adult anatomical framework of cortical connectivity, the maximal lateral distance of reconnection is limited, and the probability to encounter spiking cells decreases with increasing distance inside the LPZ. However, this recording probability was significantly increased after 1 year.