Key Structure Research Articles

Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier.

Neuroinflammation is a pathological event associated with many neurological disorders, including dementia and stroke. The choroid plexus (ChP) is a key structure in the ventricles of the brain that secretes cerebrospinal fluid (CSF), forms a blood-CSF barrier, and responds to disease conditions by recruiting immune cells and maintaining an immune microenvironment in the brain. Despite these critical roles, the exact structural and functional changes to the ChP over post-stroke time remain to be elucidated. We induced ischemic stroke in C57BL/6J mice via transient middle cerebral artery occlusion which led to reduction of cerebral blood flow and infarct stroke. At 1-7 days post-stroke, we detected time-dependent increase in the ChP blood-CSF barrier permeability to albumin, tight-junction damage, and dynamic changes of SPAK-NKCC1 protein complex, a key ion transport regulatory system for CSF production and clearance. A transient loss of SPAK protein complex but increased phosphorylation of the SPAK-NKCC1 complex was observed in both lateral ventricle ChPs. Most interestingly, stroke also triggered elevation of proinflammatory Lcn2 mRNA and its protein as well as infiltration of anti-inflammatory myeloid cells in ChP at day 5 post-stroke. These findings demonstrate that ischemic strokes cause significant damage to the ChP blood-CSF barrier, contributing to neuroinflammation in the subacute stage.

Differential spatial transcriptome profile of the hippocampal formation of protected PSEN1 E280A familial Alzheimer’s disease cases

AbstractBackgroundWe have described two cases with ∼ 30 years of delayed disease onset among carriers of PSEN1 mutation E280A, suffering from familial Alzheimer’s disease (FAD). One case was homozygous for the ApoE Christchurch (hApoEch) mutation. This case showed sparse hyperphosphorylated tau (pTau) pathology in several cortical areas. The second case was heterozygous for the RELN‐COLBOS mutation and was globally affected by severe pTau and amyloid beta pathology, with evidence of localized cellular protection in the entorhinal cortex (EC). Here we used digital spatial profiling (DSP) transcriptomics to characterize the hippocampal formation of FAD protected cases and identify possible molecular mechanisms of protection.MethodsIn depth morphological characterization of the EC together with identification of thirteen different regions of interest (ROIs) were performed in Formalin‐fixed paraffinized 3 mm thick slides taken from the hippocampal formation (Fig. 1A) of the RELN‐COLBOS FAD case, the hApoEch FAD case, three FAD cases, and three sporadic Alzheimer’s cases (SAD). Slides were immunostained for NeuN and GFAP for morphological ROIs identification and processed for localized transcriptome analyses using the GeoMX DSP platform from Nanostring. Obtained data was processed for quality control, dimensionality reduction and differential gene expression (DGE) analyses.ResultsDimensionality reduction of transcriptomic data obtained from all ROIs and studied cases showed a distinctive distribution of ROIs belonging to both protected cases (Fig. 1B). Furthermore, DGE was observed in all sampled ROIs. ROIs such as hippocampal white matter or dentate gyri showed a higher number of differentially expressed genes due to a more homogeneous cellular composition of the ROIs (Fig. 1C). Also, EC and dentate gyrus from FAD protected cases showed distinctive molecular signatures compatible with excitatory neuronal pathways (Fig. 1D). Complementary morphological analyses showed increased neuronal density in the supragranular region of the EC in the RELN‐COLBOS FAD protected case, specifically in neuronal layer II.ConclusionOur results suggest that regardless of the protective gene conferring protection to FAD, the EC is one key protected structure with distinctive regional transcriptomic profiles suggesting the preservation of neuronal function in this region and hinting towards a possible therapeutic target in the protection against Alzheimer’s disease.

Aβ oligomers reduce neuronal plasticity in an aged animal model of Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) is characterized by the extracellular accumulation of senile plaques composed of beta‐amyloid (Aβ). Aβ oligomers (AβO) induce damage beginning with loss of synapses, followed by neurite network disorganization and neuronal death. The hippocampus is a cerebral structure and a major place of neuroplasticity and a key structure for memory processing and consolidation. Hippocampal atrophy is well documented in AD. Neuronal plasticity persists during ageing and could adaptative response to cognitive decline during ageing or dementia.Alterations in adult neuronal plasticity and synaptic dysfunctions are detected in rodent models of Alzheimer’s disease. Thus, early dysfunction in neural stem cell production and neuronal differentiation could be linked to reduced neuronal plasticity in AD.MethodIn this study, to investigate the effect of age on neurogenesis, in young (12 weeks), aged and healthy (16 months) mice and in an in vivo model of AD, based on intra‐hippocampal injection of a AβO/protofibril preparation in aged (16 months) mice.Proliferation of cells (BrdU, Ki67), differentiation (DCX) and maturation (NeuN) into neurons were studied in the dendate gyrus of mice. Activation of glial cells was also assessed by immunohistochemistry. In addition, cognitive performance of mice were assessed using the Y‐maze test (short‐term spatial memory) in the same animal.ResultOur results show a decrease in neurogenesis in aged mice compared to young mice. Injection of AβO in the CA1 area was also associated with decreased neurogenesis in the dentate gyrus, neuroinflammation and to reduce performance in the Y‐maze test.This reduction in neuroblast generation was revealed by a decrease in the number of BrdU(+), Ki67(+) and DCX(+) cells in the dentate gyrus.ConclusionWe evidenced a decreased in neuronal plasticity in aging which is exacerbated in our in vivo model of AD and connected to cognitive decline.

Extracellular Tau Oligomers Damage the Axon Initial Segment by an Endogenous Tau‐Dependent Mechanism

AbstractBackgroundNeuronal polarity and synaptic connectivity are compromised in Alzheimer’s disease (AD) and other tauopathies. The axon initial segment (AIS) is a key structure for regulating polarity and functions of neurons. It occupies the first 20‐60 µm of the axon, comprises a diffusion barrier that segregates axon‐enriched from somatodendritic‐enriched molecules, and has a high concentration of voltage‐gated ion channels that generate action potentials. Extracellular amyloid‐β oligomers compromise AIS integrity. However, effects on the AIS of toxic tau species, including extracellular oligomers (xcTauOs) that spread tau pathology from neuron to neuron by a prion‐like process, whereas unknown. Therefore, we wanted to test the hypothesis that AIS structure is sensitive to xcTauOs.MethodPrimary cortical neurons derived from either wild type (WT), or tau knockout (KO) mice were exposed to xcTauOs or vehicle. Quantitative western blotting and immunofluorescence microscopy with an antibody against the AIS‐enriched protein TRIM46 was used to monitor effects on the AIS. The same methods were also used to compare TRIM46 and two other AIS proteins, ankyrin‐G and neurofascin‐186 in human hippocampal tissue obtained from AD and age‐matched non‐AD donors.ResultIn cultured WT, but not TKO neurons, xcTauOs cause a trend toward AIS shortening and reduce the concentration of the resident AIS protein, TRIM46, without affecting total TRIM46 levels. Lentiviral‐driven human tau expression in tau KO neurons rescues TRIM46 sensitivity to xcTauOs. In human AD hippocampus, AIS length and TRIM46 concentration within the AIS are reduced in neurons containing neurofibrillary tangles (NFTs), without affecting the overall protein levels of multiple resident AIS proteins.ConclusionThese collective findings demonstrate that in cultured neurons, xcTauOs cause partial AIS damage by a mechanism dependent on intracellular tau, thereby raising the possibility that AIS reduction in AD is caused by xcTauOs working in concert with endogenous neuronal tau.

Investigating the Biological Composition and Injurious Tendencies of the Rotator Cuff Muscles

The construction of our human anatomy is one of great importance. In the grand scheme of the rotational torque that our skeletomuscular body exerts, one such key structure is the Rotator Cuff Muscles. To function as a biologically sound component of the human body, the muscular composition of the Four Major Muscles: the Supraspinatus, Subscapularis, Teres Minor, and the Infraspinatus. I explored the muscular composition and substance matter of each of these 4 crucial muscles of the Rotator Cuff. Through the various connections between the movement, location (relative to the midline of the body), and the composition of tissue, an apparent connection between the muscular damage in each of these listed muscles can be observed as well.

Studies on the life, damage evolution, and crack propagation behaviors of TC18 titanium alloy under repeated impact loading

TC18 titanium alloy has been widely used as the key structure which is often subjected to repeated impacts in service in aerospace engineering. In this study, the repeated impact responses of TC18 were investigated by conducting various repeated drop hammer impact tests. Abundant microscopic characterization technologies were used to reveal the correlation between damage evolution and the impact response. The results show that the average impact fatigue life (Nf¯) of the notched three-point-bend specimen decreases exponentially with the impact energy. Microscopic observation shows that cracks nucleate at the initial 40%∼50% of Nf¯, then propagate steadily during the next 50% to 90% of Nf¯. During the last 10% of Nf¯, the cracks propagate rapidly, resulting in the failure. During crack propagation, the repeated impacts induce complex stress states in the vicinity of cracks, leading to grain refinement, phase transition, and strengthened texture. The phase transition and strengthened texture mechanisms are mainly due to the generation of the platelet-like α subgrains inside the refined grains. The results in this paper are crucial for understanding the microscopic damage and failure mechanism of TC18 under repeated impacts, which helps to establish the damage accumulation-based life prediction model in the future.

Computational models can distinguish the contribution from different mechanisms to familiarity recognition.

Familiarity is the strange feeling of knowing that something has already been seen in our past. Over the past decades, several attempts have been made to model familiarity using artificial neural networks. Recently, two learning algorithms successfully reproduced the functioning of the perirhinal cortex, a key structure involved during familiarity: Hebbian and anti-Hebbian learning. However, performance of these learning rules is very different from one to another thus raising the question of their complementarity. In this work, we designed two distinct computational models that combined Deep Learning and a Hebbian learning rule to reproduce familiarity on natural images, the Hebbian model and the anti-Hebbian model, respectively. We compared the performance of both models during different simulations to highlight the inner functioning of both learning rules. We showed that the anti-Hebbian model fits human behavioral data whereas the Hebbian model fails to fit the data under large training set sizes. Besides, we observed that only our Hebbian model is highly sensitive to homogeneity between images. Taken together, we interpreted these results considering the distinction between absolute and relative familiarity. With our framework, we proposed a novel way to distinguish the contribution of these familiarity mechanisms to the overall feeling of familiarity. By viewing them as complementary, our two models allow us to make new testable predictions that could be of interest to shed light on the familiarity phenomenon.

Laser additive manufactured NiTi-based bioinspired helicoidal structure with excellent pseudoelasticity and energy absorption capacity

Functionality-driven biomimetic additive manufacturing (AM), as a research hotspot of 3D printing field, is providing unprecedented opportunities for developing next-generation functional materials in mechanical, electrical, optical and biomedical engineering. In this work, we developed a laser AM-ed NiTi-based helicoidal structure with excellent pseudoelasticity and energy absorption capacity, inspired by the biological architecture in the exoskeleton of the crab's claw. The rotation angle θ corresponding to the misorientation of rods in adjacent layers, as the key structure parameter, was involved into the investigations on the forming quality, pseudoelastic response and fracture behavior of the laser AM-ed helicoidal structures. The results showed that an increase in θ could improve the forming accuracy of rods but decrease the porosity due to the formation of more closed pores filled with unmelted powder particles. These pores formed by the helically stacked rods had sharp edges that could trigger earlier stress concentration and phase transformation or even strain hardening during the loading process. In views of more uniform stress distribution, the helicoidal structure with θ = 36° exhibited the largest recoverable strain of 4.32 %. Regarding the deformation and fracture behavior, it was found that the helicoidal structures with small θ were inclined to exhibit an auxetic deformation behavior and a sluggish fracture process, while the ones with larger θ were prone to a buckling deformation mode and a sudden failure. Furthermore, all helicoidal structures presented excellent energy absorption properties in terms of both unit volume and unit mass values, which could be attributed to the cross-scale hierarchical structures.

Base promoted coupling of α-ketoacids and 2-substituted aromatic amines: Green synthesis of diverse benzoxazoles, benzothiazoles, quinoxalinones and benzoxazinones and its practical application

Synthesis of 2-aryl substituted benzoxazoles, benzothiazoles, and quinoxalinones via decarboxylative coupling of α-keto acids with 2-aminophenol, 2-aminothiophenol, and OPD (o-phenylenediamine), using K2CO3 as a base in water at room temperature, and as well as solvent-free grinding and the synthesis of benzoxazinones from the reaction of α-keto acids with 2-aminophenol at 60 °C have been reported. Both the protocols afforded a wide range of desired products with excellent functional group tolerance in yields of 87–99%. The major advantages of these approaches are catalyst-free protocol, short reaction times, straightforward workup, and chromatography-free processing of the products. Additionally, to test the translational demand of this methodology, the synthesis of 2-(3,5-dichlorophenyl)-6-methylbenzo[d]oxazole was carried out which is a key structure of tafamidis, a commercially available drug.

A Secret Key Classification Framework of Symmetric Encryption Algorithm Based on Deep Transfer Learning

The leakage signals, including electromagnetic, energy, time, and temperature, generated during the operation of password devices contain highly correlated key information, which leads to security vulnerabilities. In traditional encryption algorithms, the length of the key greatly affects the upper limit of its security against cracking. Regarding side-channel attacks on long-key algorithms, traditional template attack methods characterize the energy traces using multivariate Gaussian distribution during the template construction phase. The exhaustive key-guessing process is expected to consume a significant amount of time and computational resources. Therefore, to analyze the effectiveness of obtaining key values from the side information of password devices, we propose an innovative attack method based on a divide-and-conquer logical structure, targeting semi-bytes. We construct a collection of key classification submodules with symmetric correlations. By integrating a differential network model for byte-block sets and an end-to-end direct attack method, we form a holistic symmetric decision framework and propose a key classification structure based on deep transfer learning. This structure consists of three main parts: side information data acquisition, analysis of key-value effectiveness, and determination of attack positions. It employs multiple parallel symmetric subnetworks, effectively improving attack efficiency and reducing the key enumeration range. Experimental results show that the optimal attack accuracy of the network model can reach 91%, with an average attack accuracy of 78%. It overcomes overfitting issues under small sample dataset conditions.

Rice bran is a key structure affecting high nutrition and low toxicity of indica hybrid rice (Oryza sativa L.)

Rice is a staple for over half of the world's population. However, it presents toxicity risks. In this study, 23 indica rice varieties were selected; the concentration and accumulation of 18 elements in husk, bran, and milled rice were measured. The correlations between elements differ, with specific correlation networks in each grain layer, with the bran layer being the most complex. Cd and As in the bran layer accounted for 16.6% and 39.7% of the total accumulation in brown rice, respectively. Removal of the bran layer significantly reduced Fe by 35.2% and Zn by 30.2%. With the goals of high nutrition and low toxicity, the CY6709 and LLY7810 brown rice varieties were suitable without modification, whereas JY781 is best milled to reduce the risk of heavy-metal poisoning. Overall, the bran layer was enriched with both toxic and nutrient elements. To ensure greater nutrient intake, we encourage more brown rice consumption. Moreover, rice varieties should be milled according to their distributions of toxic elements to reduce safety concerns.

Altered amygdala volumes and microstructure in focal epilepsy patients with tonic-clonic seizures, ictal, and post-convulsive central apnea.

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined the volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by the presence or absence of FBTCS, ictal central apnea (ICA), and post-convulsive central apnea (PCCA). Seventy-three patients with focal impaired awareness seizures without FBTC seizures (FBTCneg group) and 30 with FBTCS (FBTCpos group) recorded during video electroencephalography (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomic and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all patients with epilepsy and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between three groups: healthy subjects, FBTCneg and FBTCpos groups. The FBTCpos group was further subdivided by the presence of ICA and PCCA, verified by VEEG. Bilateral amygdala volumes were significantly increased in the FBTCpos cohort compared to healthy controls and the FBTCneg group. Patients with recorded PCCA had the highest increase in bilateral amygdala volume of the FBTCpos cohort. Amygdala neurite density index (NDI) values were decreased significantly in both the FBTCneg and FBTCpos groups relative to healthy controls, with values in the FBTCpos group being the lowest of the two. The presence of PCCA was associated with significantly lower NDI values vs the non-apnea FBTCpos group (p = 0.004). Individuals with FBTCpos and PCCA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.

Is the Mesochori Fault a Key Structure for Understanding the Earthquake Activity during the 2021 Damasi Earthquakes in Northern Thessaly, Greece?

On 3 March 2021, an important seismic sequence started in northern Thessaly, Greece. The Damasi Seismic Sequence (DSS) deformed the western sector of the Tyrnavos Graben, which includes a major blind normal fault and the Titarisios River Graben (TRG). In this contribution, we provide fieldwork observations across the TRG and satellite radar interferometry of the faults controlling the graben. In addition, we provide a map of the active faults exposed in the TRG and palaeoseismological analyses of the Mesochori Fault, which together contribute to unravelling the seismic history of the area. DInSAR provides clear evidence of the Mesochori Fault surface rupture during the main shocks, while our palaeoseismological analyses document a long seismic history of the fault, with a mean recurrence interval of 1.0–1.5 ka and a mean slip per event of ~15 cm for the last four events reactivating the scarp. Quantitative geomorphological analyses based on real-time kinematic (RTK) measurements with global navigation satellite system (GNSS) receivers and data from UAV flight campaigns also provide evidence of postseismic activity across the Mesochori Fault. Based on these results showing that (at least) the Mesochori Fault has been reactivated several times in the latest Quaternary the seismotectonics of the TRG are discussed.

Multilingualism as a Phenomenon of Public Broadcasting (Macedonian Holding MRT)

The article focuses on the study of public broadcasting in the Republic of North Macedonia. The key structure of public broadcasting is the representation of civil society. Despite the abundance of scientific literature on this topic, there is still research interest in identifying the characteristics of different public broadcasting systems. The article analyzes the activities of the Macedonian Holding MRT, which produces television and radio content. The results of monitoring the informational and non-informational broadcasting of MRT channels (including educational and entertainment components) are presented in the article. Through content analysis of the broadcasting schedule, the specific activities of MRT are determined: the public broadcaster of North Macedonia broadcasts television and radio programs in 9 languages for all ethnic groups represented in the country. The author concludes that multilingualism gives MRT a certain exclusivity, and ethnic minorities are provided with the opportunity not only to consume television and radio content in their native language but also to be represented in the multiethnic Macedonian society.

An imaging review of the hippocampus and its common pathologies.

The hippocampus is a complex structure located in the mesial temporal lobe that plays a critical role in cognitive and memory-related processes. The hippocampal formation consists of the dentate gyrus, hippocampus proper, and subiculum, and its importance in the neural circuitry makes it a key anatomic structure to evaluate in neuroimaging studies. Advancements in imaging techniques now allow detailed assessment of hippocampus internal architecture and signal features that has improved identification and characterization of hippocampal abnormalities. This review aims to summarize the neuroimaging features of the hippocampus and its common pathologies. It provides an overview of the hippocampal anatomy on magnetic resonance imaging and discusses how various imaging techniques can be used to assess the hippocampus. The review explores neuroimaging findings related to hippocampal variants (incomplete hippocampal inversion, sulcal remnant and choroidal fissure cysts), and pathologies of neoplastic (astrocytoma and glioma, ganglioglioma, dysembryoplastic neuroepithelial tumor, multinodular and vacuolating neuronal tumor, and metastasis), epileptic (mesial temporal sclerosis and focal cortical dysplasia), neurodegenerative (Alzheimer's disease, progressive primary aphasia, and frontotemporal dementia), infectious (Herpes simplex virus and limbic encephalitis), vascular (ischemic stroke, arteriovenous malformation, and cerebral cavernous malformations), and toxic-metabolic (transient global amnesia and opioid-associated amnestic syndrome) etiologies.

A modeling study of elastoplastic rock failure regime based on finite discrete elements

Numerical simulation has become a pivotal method in geotechnical engineering for analyzing rock failure. However, traditional model lacks comprehensive elastoplastic rock characterization. Therefore, a new finite-discrete element model using the Drucker-Prager criterion and cohesive elements based on a traction-separation law to accurately simulate elastoplastic rock breaking has been built. A scratch test simulation is conducted to describe the mechanical response and failure characteristics of the rock during the cutting process. Rock failure characteristics derived from numerical simulations align closely with experimental observations. These simulations successfully replicate both the ductile and brittle regimes observed during scratch tests. Furthermore, they provide insights into the primary driving factors behind rock failure under different regimes. Variation of cutting force and specific energy obtained from the model are entirely consistent with experimental results, with the specific energy decreasing following a −0.5 power law, thus explaining the energy dissipation rule of the specific energy decrease. In brittle regime, crush zones and the resulting rough shearing surface are observed, plastic damage is also found, revealing that the cutter tip is the key structure influencing them. The model established in this paper holds significant importance for rock mechanical property evaluation and the optimization design of cutter structures.

Simulation research on erosion of downhole tools with groove structure during hydraulic fracturing

Groove structure is the key structure for designing the downhole tools. During the hydraulic fracturing, the flow channel change caused by these groove structure will lead to flow field disturbance, and thus forming the erosion caused by the mixing of solid–liquid two-phase fluid with proppant and fracturing fluid. According to the physical process of hydraulic fracturing, the erosion model of these groove structure is established based on discrete particle model, and the erosion mechanism and characteristic are systemically analyzed. The results indicate that the formation of eddy current disturbance leads to a sharp change in the flow velocity direction, causing proppant particles to impact and wear the downstream surface of the groove structure, resulting in serious erosion. The relationship between the maximum erosion rate and the displacement shows an exponential rising trend, and the larger the displacement, the greater the maximum erosion rate. The maximum erosion rate increases linearly with the increase of proppant particle concentration under different displacements, and the larger the injection displacement, the greater the influence of proppant particle concentration on the maximum erosion rate. This research can provide reference for the anti-erosion design of downhole tools with groove structure.

Bond Parameter Calibration and Crushing Process Analysis of Brown Rice Kernels

Aiming to resolve the practical problem of brown rice kernels being easily broken due to overprocessing during processing (milling and polishing), brown rice kernels of Japonica rice, after hulling, were used as the research object in this study. Firstly, through a texture meter test, the discrete element bonding parameters (Kn is normal stiffness per unit area, Kτ is tangential stiffness per unit area, Cn is critical normal stiffness, Cτ is critical shear stiffness) were obtained. Secondly, a brown rice kernels’ bonding particle model was established by EDEM, and then a second orthogonal rotational combination test was carried out to calibrate the discrete bonding parameters, Kn = 4.43 × 1012 N/m3, Kτ = 6.13 × 1011 N/m3, Cn = 2.55 × 107 Pa, and Cτ = 7.92 × 107 Pa. The error of parameter calibration was within 5%, and the results were able to reflect the actual situation more realistically. Finally, analysis of the crushing process of brown rice kernels showed that their ability to withstand shear damage was not as great as their pressure-bearing capacity. The design of the relevant mechanism and the setting of parameters should be based on the critical shear stiffness of brown rice kernels, and the actual shear force Fτ* set during the processing should be smaller than the theoretical critical shear force Fτ (Fτ* < Fτ = 9.11 N). This study can provide a theoretical basis for optimizing the key structure and operating parameters of rice milling machines and polishing machines to effectively solve the practical problem of increased crushing of brown rice kernels due to overprocessing.

Corpus callosum in children with neurodevelopmental delay: MRI standard qualitative assessment versus automatic quantitative analysis

BackgroundThe corpus callosum (CC) is a key brain structure. In children with neurodevelopmental delay, we compared standard qualitative radiological assessments with an automatic quantitative tool.MethodsWe prospectively enrolled 73 children (46 males, 63.0%) with neurodevelopmental delay at single university hospital between September 2020 and September 2022. All of them underwent 1.5-T brain magnetic resonance imaging (MRI) including a magnetization-prepared 2 rapid acquisition gradient echoes − MP2RAGE sequence. Two radiologists blindly reviewed the images to classify qualitatively the CC into normal, hypoplasic, hyperplasic, and/or dysgenetic classes. An automatic tool (QuantiFIRE) was used to provide brain volumetry and T1 relaxometry automatically as well as deviations of those parameters compared with a healthy age-matched cohort. The MRI reference standard for CC volumetry was based on the Garel et al. study. Cohen κ statistics was used for interrater agreement. The radiologists and QuantiFIRE’s diagnostic accuracy were compared with the reference standard using the Delong test.ResultsThe CC was normal in 42 cases (57.5%), hypoplastic in 20 cases (27.4%), and hypertrophic in 11 cases (15.1%). T1 relaxometry values were abnormal in 26 children (35.6%); either abnormally high (18 cases, 24.6%) or low (8 cases, 11.0%). The interrater Cohen κ coefficient was 0.91. The diagnostic accuracy of the QuantiFIRE prototype was higher than that of the radiologists for hypoplastic and normal CC (p = 0.003 for both subgroups, Delong test).ConclusionsAn automated volumetric and relaxometric assessment can assist the evaluation of brain structure such as the CC, particularly in the case of subtle abnormalities.Relevance statementAutomated brain MRI segmentation combined with statistical comparison to normal volume and T1 relaxometry values can be a useful diagnostic support tool for radiologists.Key points• Corpus callosum abnormality detection is challenging but clinically relevant.• Automated quantitative volumetric analysis had a higher diagnostic accuracy than that of visual appreciation of radiologists.• Quantitative T1 relaxometric analysis might help characterizing corpus callosum better.Graphical

Mouse frontal cortex nonlinearly encodes stimuli, choices, and outcomes

Frontal area MOs (secondary motor area) is a key brain structure in rodents for making decisions based on sensory evidence and on reward value. Its neurons can encode sensory stimuli, upcoming choices, expected rewards, ongoing actions, and recent outcomes. However, the information encoded, and the nature of the resulting code, may depend on the task being performed. We recorded MOs population activity using two-photon calcium imaging, in a task requiring mice to integrate sensory evidence with reward value. Mice turned a wheel to report the location of a visual stimulus following a delay period, to receive a reward whose size varied over trial blocks. MOs neurons encoded multiple task variables, but not all of those seen in other tasks. In the delay period, MOs neurons strongly encoded the stimulus side but did not significantly encode the reward-size block. A correlation of MOs activity with upcoming choice could be explained by a common effect of stimuli on those two correlates. After the wheel turn and the feedback, the MOs population encoded choice side and choice outcome jointly and nonlinearly according to an exclusive-or (XOR) operation. This nonlinear operation would allow a downstream linear decoder to infer the correct choice side (i.e., the side that would have been rewarded) even on zero contrast trials, when there had been no visible stimulus. These results indicate that MOs neurons flexibly encode some but not all variables that determine behavior, depending on task. Moreover, they reveal that MOs activity can reflect a nonlinear combination of these behavioral variables, allowing simple linear inference of task events that would not have been directly observable.