New pyridine-based chalcones and pyrazolines with anticancer, antibacterial, and antiplasmodial activities.

New pyridine-based chalcones 4a-h and pyrazolines 5a-h (N-acetyl), 6a-h (N-phenyl), and 7a-h (N-4-chlorophenyl) were synthesized and evaluated by the National Cancer Institute (NCI) against 60 different human cancer cell lines. Pyrazolines 6a, 6c-h, and 7a-h satisfied the pre-determined threshold inhibition criteria, obtaining that compounds 6c and 6f exhibited high antiproliferative activity, reaching submicromolar GI50 values from 0.38 to 0.45 µM, respectively. Moreover, compound 7g (4-CH3) exhibited the highest cytostatic activity of these series against different cancer cell lines from leukemia, nonsmall cell lung, colon, ovarian, renal, and prostate cancer, with LC50 values ranging from 5.41 to 8.35 µM, showing better cytotoxic activity than doxorubicin. Furthermore, the compounds were tested for antibacterial and antiplasmodial activities. Chalcone 4c was the most active with minimal inhibitory concentration (MIC) = 2 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA), while the pyrazoline 6h showed a MIC = 8 µg/mL against Neisseria gonorrhoeae. For anti-Plasmodium falciparum activity, the chalcones display higher activity with EC50 values ranging from 10.26 to 10.94 µg/mL. Docking studies were conducted against relevant proteins from P. falciparum, exhibiting the minimum binding energy with plasmepsin II. In vivo toxicity assay in Galleria mellonella suggests that most compounds are low or nontoxic.

New bands in the sleep stages of spider monkeys (Ateles geoffroyi): Electroencephalographic correlations and spatial distribution.

The study of electroencephalographic (EEG) signals in nonhuman primates has led to important discoveries in neurophysiology and sleep behavior. Several studies have analyzed digital EEG data from primate species with prehensile tails, like the spider monkey, and principal component analysis has led to the identification of new EEG bands and their spatial distribution during sleep and wakefulness in these monkeys. However, the spatial location of the EEG correlations of these new bands during the sleep-wake cycle in the spider monkey has not yet been explored. Thus, the objective of this study was to determine the spatial distribution of EEG correlations in the new bands during wakefulness, rapid eye movement (REM) sleep, and non-REM sleep in this species. EEG signals were obtained from the scalp of six monkeys housed in experimental conditions in a laboratory setting. Regarding the 1-21 Hz band, a significant correlation between left frontal and central regions was recorded during non-REM 2 sleep. In the REM sleep, a significant correlation between these cortical areas was seen in two bands: 1-3 and 3-13 Hz. This reflects a modification of the degree of coupling between the cortical areas studied, associated with the distinct stages of sleep. The intrahemispheric EEG correlation found between left perceptual and motor regions during sleep in the spider monkey could indicate activation of a neural circuit for the processing of environmental information that plays a critical role in monitoring the danger of nocturnal predation.

In silico prediction and in vitro assessment of novel heterocyclics with antimalarial activity.

The development of new antimalarials is paramount to keep the goals on reduction of malaria cases in endemic regions. The search for quality hits has been challenging as many inhibitory molecules may not progress to the next development stage. The aim of this work was to screen an in-house library of heterocyclic compounds (HCUV) for antimalarial activity combining computational predictions and phenotypic techniques to find quality hits. The physicochemical determinants, pharmacokinetic properties (ADME), and drug-likeness of HCUV were evaluated in silico, and compounds were selected for structure-based virtual screening and in vitro analysis. Seven Plasmodium target proteins were selected from the DrugBank Database, and ligands and receptors were processed using UCSF Chimera and Open Babel before being subjected to docking using Autodock Vina and Autodock 4. Growth inhibition of P. falciparum (3D7) cultures was tested by SYBR Green assays, and toxicity was assessed using hemolytic activity tests and the Galleria mellonella in vivo model. From a total of 792 compounds, 341 with good ADME properties, drug-likeness, and no interference structures were subjected to in vitro analysis. Eight compounds showed IC50 ranging from 0.175 to 0.990 µM, and active compounds included pyridyl-diaminopyrimido-diazepines, pyridyl-N-acetyl- and pyridyl-N-phenyl-pyrazoline derivatives. The most potent compound (UV802, IC50 0.178 µM) showed no toxicophoric and was predicted to interact with P. falciparum 1-cysperoxidredoxin (PfPrx1). For the remaining 7 hits (IC50 < 1 µM), 3 showed in silico binding to PfPrx1, one was predicted to bind the haloacid dehalogenase-like hydrolase and plasmepsin II, and one interacted with the plasmodial heat shock protein 90.

EEG coherence and power spectra during REM sleep related to melatonin intake in mild-to-moderate Alzheimer's disease: a pilot study.

It has been reported that melatonin diminishes rapid eye movement (REM) sleep latency in patients with Alzheimer's disease (AD). Pharmacological studies suggest that melatonin promotes prompt sleep installation through interaction with GABA receptors, and that it is associated with acute suppression of neural electrical activity. Nevertheless, melatonin's effects on electroencephalographic (EEG) activity related to REM sleep onset in AD patients have not been analyzed. Thus, in this pilot study we analyzed the effects of melatonin on EEG activity during the first episode of REM sleep in eight patients treated with 5-mg of fast-release melatonin.During a single-blind, placebo-controlled study, polysomnographic recordings were obtained from frontal, central, temporal, and occipital scalp derivations. REM sleep latency, as well as the relative power (RP) and EEG coherences of six EEG bands, were compared between the placebo and melatonin conditions.Results showed that melatonin intake in AD patients decreased REM sleep onset, and that this was associated with lower RP and coherence of the ß and γ EEG bands.The possibility that the inhibitory GABAergic pathways related to REM sleep generation are well-preserved in mild-to-moderate AD is discussed. We conclude that the short REM sleep onset related to melatonin intake in AD patients is associated with a significant decrease in both RP and EEG coherence, mainly in the fast frequencies.

Effects of emotional congruency and task complexity on decision-making.

The heuristic approach to decision-making holds that the selection process becomes more efficient when part of the information available is ignored. One element involved in selecting information is emotional valence. If emotional congruency is related to simplified decision-making strategies, then the interaction of this factor with task complexity should exist. The present study explored how factors of this nature influence decision-making efficiency. We hypothesized that emotional congruency would have a positive effect on task execution and that the magnitude of that effect would increase with greater task complexity because in that condition the amount of information to be processed is greater, meaning that a heuristic approach to the problem would be more efficient. We design a decision in browser decision-making task in which participants had to select emotional images to gain points. Depending on the correlation between emotional valence and in-task image value, we defined three emotional congruency conditions: direct, null, and inverse. Our results show that distinct types of emotional congruency have differential effects on behavior. While direct congruency-enhanced overall decision-making performance, inverse congruency interacted with task complexity to modify the pace at which task feedback affected behavior.

Disentangling the variability of the superficial white matter organization using regional-tractogram-based population stratification.

Each variation of the cortical folding pattern implies a particular rearrangement of the geometry of the fibers of the underlying white matter. While this rearrangement only impacts the ends of the long pathways, it may affect most of the trajectory of the short bundles. Therefore, mapping the short fibers of the human brain using diffusion-based tractography requires a dedicated strategy to overcome the variability of the folding patterns. In this paper, we propose a fiber-based stratification strategy splitting the population into homogeneous groups for disentangling the superficial white matter bundle organization. This strategy introduces a new refined fiber distance which includes angular considerations for inferring fine-grained atlases of the short bundles surrounding a specific sulcus and a subtractogram distance that quantifies the similitude between fiber sets of two different subjects. The stratification splits the population into groups with similar regional fiber organization using manifold learning. We first successfully test the hypothesis that the main source of variability of the regional fiber organization is the variability of the regional folding pattern. Then, in each group, we proceed with the automatic identification of the most stable bundles, at a higher granularity level than what can be achieved with the non-stratified whole population, enabling the disentanglement of the very variable configuration of the short fibers. Finally, the method searches for bundle correspondence across groups to build a population level atlas. As a proof of concept, the atlas refinement achieved by this strategy is illustrated for the fibers that surround the central sulcus and the superior temporal sulcus using the HCP dataset.

Pentylenetetrazol-induced seizures are followed by a reduction in the multiunitary activity of hippocampal CA1 pyramidal neurons in adult rats.

Pentylenetetrazol (PTZ) blocks the inhibitory action of GABA, triggering a Glu-mediated hyperexcitation of the dendritic spines in hippocampal CA1 pyramidal neurons that leads to the generation of epileptiform seizures. The aim of this work was to determine the effect of PTZ on the electrical activity of the hippocampal pyramidal neurons in male rats. Bipolar electrodes were implanted stereotaxically in the right and left hippocampal CA1 fields of adults, and PTZ (65 mg/kg) was administered i.p. Simultaneous recordings of the field activity and the firing rate (multiunitary activity, MUA) were analyzed at 10, 20, and 30 min post-administration of PTZ. Only rats that presented tonic-clonic seizures during the first 1-5 min after PTZ treatment were included in the study. The recordings of the field activity were analyzed in 4 frequency bands. In both the right and left hippocampal CA1 fields, the relative power corresponding to the slow waves (4-7 Hz) increased, while in the bands 13-30 Hz and 31-50 Hz, it decreased at 10, 20, and 30 min post-PTZ. MUA recordings were analyzed at four levels. The highest levels corresponded to larger amplitudes of the action potentials in the pyramidal neurons. The firing rates of the PTZ-treated rats did not differ from baseline but presented a significant decrement at 10, 20, and 30 min post-PTZ. The decreased firing rate of the hippocampal CA1 pyramidal neurons after PTZ treatment could be associated with plastic changes of dendritic spines along with some microenvironmental adaptations at synaptic level, after neuronal PTZ-mediated hyperexcitation.

Prenatally stress-exposed male rats present lower theta prefrontal activity during attention behaviors to receptive females.

Prenatal stress affects brain functionality and sexual behavior. The medial prefrontal cortex (mPFC) participates in the integration and processing of sexual stimuli. Electroencephalographic (EEG) theta activity has been associated with attention as well as rewarding and sexually motivated states. Considering that the induction of sexual motivation requires attention to, and the adequate processing of, sexual stimuli, this study aimed to evaluate the effects of exposure to stress during the prenatal period on EEG activity in the mPFC during nose pokes in adulthood, actions which are indicators of attention to a receptive female. Eighteen sexually experienced male rats were used, nine stressed prenatally by immobilization during days 14-21 of gestation (stress-exposed group). The other nine formed the control group. All rats were implanted bilaterally in the mPFC (specifically in prelimbic areas) and were allowed one intromission with a receptive female to induce a sexually motivated state before the experimental session. During this session, both nose pokes and non-contact erections in the male rats were evaluated in the presence of an inaccessible receptive female. EEGs were recorded only during nose pokes. The stress-exposed group presented lower nose poke duration, fewer non-contact erections, and lower relative power of the theta band (4-7 Hz) in both prefrontal areas. Considering that the prevalence of this band is associated with attention and motivational processes, these data confirm the deleterious effect of prenatal stress on attention and sexual activation to sexually relevant stimuli in male rats during adulthood.

Lay summariesPrenatal stress diminishes attention and activation behaviors in receptive females.Prenatal stress decreases prefrontal activation in the presence of receptive females.Prenatal stress decreases prefrontal theta rhythms in male rats.

ABrainVis: an android brain image visualization tool.

BACKGROUND: The visualization and analysis of brain data such as white matter diffusion tractography and magnetic resonance imaging (MRI) volumes is commonly used by neuro-specialist and researchers to help the understanding of brain structure, functionality and connectivity. As mobile devices are widely used among users and their technology shows a continuous improvement in performance, different types of applications have been designed to help users in different work areas. RESULTS: We present, ABrainVis, an Android mobile tool that allows users to visualize different types of brain images, such as white matter diffusion tractographies, represented as fibers in 3D, segmented fiber bundles, MRI 3D images as rendered volumes and slices, and meshes. The tool enables users to choose and combine different types of brain imaging data to provide visual anatomical context for specific visualization needs. ABrainVis provides high performance over a wide range of Android devices, including tablets and cell phones using medium and large tractography datasets. Interesting visualizations including brain tumors and arteries, along with fiber, are given as examples of case studies using ABrainVis. CONCLUSIONS: The functionality, flexibility and performance of ABrainVis tool introduce an improvement in user experience enabling neurophysicians and neuroscientists fast visualization of large tractography datasets, as well as the ability to incorporate other brain imaging data such as MRI volumes and meshes, adding anatomical contextual information.

Topographic distribution of the EEG ad hoc broad bands during sleep and wakefulness in the spider monkey (Ateles Geoffroyi).

There is evidence that research on sleep among New World monkeys may provide important knowledge related to the evolution of sleep more broadly in the primate order. Digital electroencephalographic (EEG) analyses provide essential knowledge on sleep in the spider monkey. Recently, specific EEG bands related to sleep in these animals have been obtained using principal component analysis, but the exact spatio-temporal distribution of these EEG bands in this species has not yet been analyzed. This study determined the topographic distribution of the EEG spectral power of ad hoc broad bands during rapid eye movement sleep, nonrapid eye movement sleep, and wakefulness. Superficial EEG activity was obtained from the occipital, frontal, and central areas of six young adult male monkeys housed in a laboratory. During wakefulness, occipital areas showed high absolute power in the 1-3, 3-12, and 11-30 Hz ranges, while during nonrapid eye movement 1 sleep the highest absolute power was in the 13-30 Hz range. During nonrapid eye movement 3 sleep, frontal and central areas showed a high absolute power in the 18-19 Hz range. Finally, the right central area showed a high absolute power in the 20-30 Hz range during rapid eye movement sleep. This topographic distribution of EEG bands could represent the brain organization required for arousal and mnemonic processing during sleep in the spider monkey.

Melatonin effects on EEG activity during non-rapid eye movement sleep in mild-to-moderate Alzheimer´s disease: a pilot study.

INTRODUCTION: There is evidence to suggest that melatonin diminishes non-rapid eye movement sleep (NREMS) latency in patients with Alzheimer´s disease (AD). However, melatonin's effects on cortical activity during NREMS in AD have not been studied. The objective of this research was to analyze the effects of melatonin on cortical activity during the stages of NREMS in 8 mild-to-moderate AD patients that received 5-mg of fast-release melatonin. METHODS: During a single-blind, placebo-controlled crossover study, polysomnographic recordings were obtained from C3-A1, C4-A2, F7-T3, F8-T4, F3-F4 and O1-O2. Also, the relative power (RP) and EEG coherences of the delta, theta, alpha1, alpha2, beta1, beta2 and gamma bands were calculated during NREMS-1, NREMS-2 and NREMS-3. These sleep latencies and all EEG data were then compared between the placebo and melatonin conditions. RESULTS: During NREMS-2, a significant RP increase was observed in the theta band of the left-central hemisphere. During NREMS-3, significant RP decreases in the beta bands were recorded in the right-central hemisphere, compared to the placebo group. After melatonin administration, significant decreases of EEG coherences in the beta2, beta1 and gamma bands were observed in the right hemisphere during NREMS-3. DISCUSSION: We conclude that short NREMS onset related to melatonin intake in AD patients is associated with a significant RP increase in the theta band and a decrease in RP and EEG coherences in the beta and gamma bands during NREMS-3. These results suggest that the GABAergic pathways are preserved in mild-to-moderate AD.

Phytotoxicity test in check: Proposition of methodology for comparison of different method adaptations usually used worldwide.

Seed germination tests have been widely used in recent years to indicate the toxicity levels of samples of organic compounds, biosolids, residues and effluents. Lactuca sativa L, commonly known as lettuce, has been one of the main indicative species for these tests due to its high sensitivity to low levels of toxicity, when compared to other seeds and also because it is cultivated worldwide. Although this type of analysis or essay is being widely used, it is necessary to reflect on the various adaptations of methods used by different researchers worldwide. This work presents an innovative methodology that makes it possible to compare the different phytotoxicity methods currently used in the world, through four stages that include the coefficient of variation (CV) as the main classification criterion, also counting on an eliminatory criterion. The existence of a significant difference (P value < 0.05) between the evaluated tests was proven. The phytotoxicity test that presented the lowest CV was T8 (test with lettuce seeds at 25 °C, 60 min agitation, resting overnight, 5 mL of sample on the plate, 90 mm size plate). It has concluded that not all adaptations of this type of test are reliable. It has also concluded that there is a lack of standardization for the phytotoxicity test on a global scale, which makes the various researchers in the field end up promoting variations, adaptations for the phytotoxicity test; therefore, there is an urgent need for ways to compare these variations, as the innovation proposed by this work. With a single standard methodology, we conclude that it will make it possible to compare phytotoxicity in samples directly between countries and continents, being able to generate a worldwide panorama of phytotoxicity, publicizing and comparing the standardized phytotoxicity levels in each region.

Superficial white matter: A review on the dMRI analysis methods and applications.

The mapping of human brain connections is still an on going task. Unlike deep white matter (DWM), which has been extensively studied and well documented, superficial white matter (SWM) has been often left aside. Improving our understanding of the SWM is an important goal for a better understanding of the brain network and its relation to several pathologies. The shape and localization of these short bundles present a high variability across subjects. Furthermore, the small diameter of most superficial bundles and partial volume effects induced by their proximity to the cortex leads to complex tratography issues. Therefore, the mapping of SWM bundles and the use of the resulting atlases for clinical studies requiere dedicated methodologies that are reviewed in this paper.

Principal component analysis of electroencephalographic activity during sleep and wakefulness in the spider monkey (Ateles geoffroyi).

The study of electroencephalographic (EEG) activity during sleep in the spider monkey has provided new insights into primitive arboreal sleep physiology and behavior in anthropoids. Nevertheless, studies conducted to date have maintained the frequency ranges of the EEG bands commonly used with humans. The aim of the present work was to determine the EEG broad bands that characterize sleep and wakefulness in the spider monkey using principal component analysis (PCA). The EEG activity was recorded from the occipital, central, and frontal EEG derivations of six young-adult male spider monkeys housed in a laboratory setting. To determine which frequencies covaried and which were orthogonally independent during sleep and wakefulness, the power EEG spectra and interhemispheric and intrahemispheric EEG correlations from 1 to 30 Hz were subjected to PCA. Findings show that the EEG bands detection differed from those reported previously in both spider monkeys and humans, and that the 1-3 and 2-13 Hz frequency ranges concur with the oscillatory activity elucidated by cellular recordings of subcortical regions. Results show that applying PCA to the EEG spectrum during sleep and wakefulness in the spider monkey led to the identification of frequencies that covaried with, and were orthogonally independent of, other frequencies in each behavioral vigilance state. The new EEG bands differ from those used previously with both spider monkeys and humans. The 1-3 and 2-13 Hz frequency ranges are in accordance with the oscillatory activity elucidated by cellular recordings of subcortical regions in other mammals.

EEG correlation during the solving of simple and complex logical-mathematical problems.

Solving logical-mathematical word problems is a complex task that requires numerous cognitive operations, including comprehension, reasoning, and calculation. These abilities have been associated with activation of the parietal, temporal, and prefrontal cortices. It has been suggested that the reasoning involved in solving logical-mathematical problems requires the coordinated functionality of all these cortical areas. In this study was evaluated the activation and electroencephalographic (EEG) correlation of the prefrontal, temporal, and parietal regions in young men while solving logical-mathematical word problems with two degrees of difficulty: simple and complex. During the solving of complex problems, higher absolute power and EEG correlation of the alpha and fast bands between the left frontal and parietal cortices were observed. A temporal deactivation and functional decoupling of the right parietal-temporal cortices also were obtained. Solving complex problems probably require activation of a left prefrontal-parietal circuit to maintain and manipulate multiple pieces of information. The temporal deactivation and decreased parietal-temporal correlation could be associated to text processing and suppression of the content-dependent reasoning to focus cognitive resources on the mathematical reasoning. Together, these findings support a pivotal role for the left prefrontal and parietal cortices in mathematical reasoning and of the temporal regions in text processing required to understand and solve written mathematical problems.

Local structural connectivity is associated with social cognition in autism spectrum disorder.

The current theory implying local, short-range overconnectivity in autism spectrum disorder, contrasting with long-range underconnectivity, is based on heterogeneous results, on limited data involving functional connectivity studies, on heterogeneous paediatric populations and non-specific methodologies. In this work, we studied short-distance structural connectivity in a homogeneous population of males with high-functioning autism spectrum disorder and used a novel methodology specifically suited for assessing U-shaped short-distance tracts, including a recently developed tractography-based atlas of the superficial white matter fibres. We acquired diffusion-weighted MRI for 58 males (27 subjects with high-functioning autism spectrum disorder and 31 control subjects) and extracted the mean generalized fractional anisotropy of 63 short-distance tracts. Neuropsychological evaluation included Wechsler Adult Intelligence Scale IV (WAIS-IV), Communication Checklist-Adult, Empathy Quotient, Social Responsiveness Scale and Behaviour Rating Inventory of Executive Function-Adult (BRIEF-A). In contradiction with the models of short-range over-connectivity in autism spectrum disorder, we found that patients with autism spectrum disorder had a significantly decreased anatomical connectivity in a component comprising 13 short tracts compared to controls. Specific short-tract atypicalities in temporal lobe and insula were significantly associated with clinical manifestations of autism spectrum disorder such as social awareness, language structure, pragmatic skills and empathy, emphasizing their importance in social dysfunction. Short-range decreased anatomical connectivity may thus be an important substrate of social deficits in autism spectrum disorder, in contrast with current models.

"Plis de passage" Deserve a Role in Models of the Cortical Folding Process.

Cortical folding is a hallmark of brain topography whose variability across individuals remains a puzzle. In this paper, we call for an effort to improve our understanding of the pli de passage phenomenon, namely annectant gyri buried in the depth of the main sulci. We suggest that plis de passage could become an interesting benchmark for models of the cortical folding process. As an illustration, we speculate on the link between modern biological models of cortical folding and the development of the Pli de Passage Frontal Moyen (PPFM) in the middle of the central sulcus. For this purpose, we have detected nine interrupted central sulci in the Human Connectome Project dataset, which are used to explore the organization of the hand sensorimotor areas in this rare configuration of the PPFM.

Verbal and visuospatial working memory during pregnancy: EEG correlation between the prefrontal and parietal cortices.

Pregnancy is a dynamic process during which significant cognitive changes take place. It has been suggested that working memory (WM) is affected during gestation as a result of functional changes among cortical areas, such as the prefrontal and parietal cortices. This study examined cortical electroencephalographic correlations (rEEG) during performance of WM tasks in each trimester of pregnancy. Forty women were divided into 4 groups: first (T1), second (T2), and third (T3) trimester of pregnancy, and a control group of non-pregnant women. Electroencephalographic activity (EEG) was recorded from the frontopolar, dorsolateral and parietal cortices during performance of one verbal and one visuospatial working memory task. Only groups T2 and T3 showed increased onset latency in the visuospatial WM. During the verbal WM task, the T1 group showed a higher correlation between dorsolateral areas in the theta and alpha bands, as well as a lower left prefrontal-parietal correlation in the gamma band. During the visuospatial WM task, the T1 and T3 groups showed a higher left EEG correlation in the delta and alpha1 bands, whereas T2 presented a higher right prefrontal-parietal correlation in the gamma band. Although pregnancy had only a subtle effect on the visuospatial WM task, these different patterns of cortical synchronization in each trimester of pregnancy could represent adaptive mechanisms that enabled the pregnant women to focus their attention and use more cognitive resources and so adequately solve the WM tasks.

Cortical beta EEG oscillations related to changes in muscle tone activity during sleep in spider monkey (Ateles geoffroyi).

BACKGROUND: The physiological mechanisms that allow for sleeping in a vertical position, which is primordial for arboreal primates, have not been studied yet. METHODS: A non-invasive polysomnographic study of 6 spider monkeys (Ateles geoffroyi) was conducted. The relative beta power of the motor cortex and its linear relation with muscle tone in the facial mentalis muscle and the abductor caudae medialis muscle of the tail during wakefulness and sleep stages were calculated. RESULTS: A strong negative linear relationship (r = -.8, P = .03) was found between the relative power of the beta2 band in the left motor cortex and abductor caudae medialis muscle tone during delta sleep. CONCLUSIONS: The left motor cortex, through beta2 band activity, interacts with abductor caudae medialis muscle tonicity during delta sleep. This interaction takes part in the mechanisms that regulate the sleep postures.

Reproducibility of superficial white matter tracts using diffusion-weighted imaging tractography.

Human brain connection map is far from being complete. In particular the study of the superficial white matter (SWM) is an unachieved task. Its description is essential for the understanding of human brain function and the study of pathogenesis triggered by abnormal connectivity. In this work we automatically created a multi-subject atlas of SWM diffusion-based bundles of the whole brain. For each subject, the complete cortico-cortical tractogram is first split into sub-tractograms connecting pairs of gyri. Then intra-subject shape-based fiber clustering performs compression of each sub-tractogram into a set of bundles. Proceeding further with shape-based clustering provides a match of the bundles across subjects. Bundles found in most of the subjects are instantiated in the atlas. To increase robustness, this procedure was performed with two independent groups of subjects, in order to discard bundles without match across the two independent atlases. Finally, the resulting intersection atlas was projected on a third independent group of subjects in order to filter out bundles without reproducible and reliable projection. The final multi-subject diffusion-based U-fiber atlas is composed of 100 bundles in total, 50 per hemisphere, from which 35 are common to both hemispheres.