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1.
Neuron ; 112(20): 3396-3411.e6, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39178859

RESUMEN

We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (n = 34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bimodal distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex, and complex sulci were less heritable and typically located in heteromodal cortex. Aligning these results with an independent fetal brain MRI cohort (n = 228; 21-36 gestational weeks), we found that linear sulci formed earlier, and the earliest and latest-forming sulci had the least between-adult variation. Using high-resolution maps of cortical gene expression, we found that linear sulcation is mechanistically underpinned by trans-sulcal gene expression gradients enriched for developmental processes.


Asunto(s)
Imagen por Resonancia Magnética , Humanos , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Femenino , Anciano de 80 o más Años , Anciano , Masculino , Corteza Cerebral/diagnóstico por imagen , Feto , Encéfalo/diagnóstico por imagen , Encéfalo/embriología , Regulación del Desarrollo de la Expresión Génica , Estudios de Cohortes
2.
Neurology ; 103(5): e209749, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39133883

RESUMEN

BACKGROUND AND OBJECTIVES: Brain MRI abnormalities and increases in neurofilament light chain (NfL) have mostly been observed in cross-sectional studies before ataxia onset in polyglutamine spinocerebellar ataxias. Our study aimed to identify longitudinal changes in biological, clinical, and/or imaging biomarkers in spinocerebellar ataxia (SCA) 2 and SCA7 carriers over 1 year. METHODS: We studied SCA2 and SCA7 carriers and controls (expansion-negative relatives) at the Paris Brain Institute. Inclusion criteria included Scale for the Assessment and Rating of Ataxia (SARA) scores between 0 and 15. Assessments at baseline, 6 months, and 12 months comprised neurologic, quality of life, orofacial motor, neuropsychological, and ophthalmologic examinations, along with gait and oculomotor recordings, brain MRI, CSF, and blood sampling. The primary outcome was the longitudinal change in these assessments over 1 year. RESULTS: We included 15 SCA2 carriers, 15 SCA7 carriers, and 10 controls between May 2020 and April 2021. At baseline, the ages were similar (41 [37, 46] for SCA2, 38 [28.5, 39.8] for SCA7, and 39.5 [31, 54.5] for controls, p = 0.78), as well the sex (p = 0.61); SARA scores were low but different (4 [1.25, 6.5] in SCA2, 2 [0, 11.5] in SCA7, and 0 in controls, p < 0.01). Pons and medulla volumes were smaller in SCAs (p < 0.05) and cerebellum volume only in SCA2 (p = 0.01). Plasma NfL levels were higher in SCA participants (SCA2: 14.2 pg/mL [11.52, 15.89], SCA7: 15.53 [13.27, 23.23]) than in controls (4.88 [3.56, 6.17], p < 0.001). After 1-year follow-up, in SCA2, there was significant pons (-144 ± 60 mm3) and cerebellum (-1,508 ± 580 mm3) volume loss and a worsening of gait assessment; in SCA7, SARA score significantly increased (+1.3 ± 0.4) and outer retinal nuclear layer thickness decreased (-15.4 ± 1.6 µm); for both SCA groups, the orofacial motor assessment significantly worsened. For preataxic and early ataxic carriers, the strongest longitudinal deterioration on outcome measures was orofacial motility in SCA2 and retinal thickness in SCA7. DISCUSSION: Despite the limitation of the small sample size, we detected annual changes in preataxic and early ataxic SCA individuals across brain MRI imaging, clinical scores, gait parameters, and retinal thickness. These parameters could serve as potential end points for future therapeutic trials in the preataxic phase. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT04288128.


Asunto(s)
Biomarcadores , Imagen por Resonancia Magnética , Proteínas de Neurofilamentos , Ataxias Espinocerebelosas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/genética , Adulto , Biomarcadores/sangre , Estudios Longitudinales , Proteínas de Neurofilamentos/sangre , Heterocigoto , Ataxina-7/genética , Ataxina-2/genética , Progresión de la Enfermedad , Encéfalo/diagnóstico por imagen
3.
Brain Struct Funct ; 229(8): 1943-1977, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39020215

RESUMEN

Diffusion MRI tractography (dMRI) has fundamentally transformed our ability to investigate white matter pathways in the human brain. While long-range connections have extensively been studied, superficial white matter bundles (SWMBs) have remained a relatively underexplored aspect of brain connectivity. This study undertakes a comprehensive examination of SWMB connectivity in both the human and chimpanzee brains, employing a novel combination of empirical and geometric methodologies to classify SWMB morphology in an objective manner. Leveraging two anatomical atlases, the Ginkgo Chauvel chimpanzee atlas and the Ginkgo Chauvel human atlas, comprising respectively 844 and 1375 superficial bundles, this research focuses on sparse representations of the morphology of SWMBs to explore the little-understood superficial connectivity of the chimpanzee brain and facilitate a deeper understanding of the variability in shape of these bundles. While similar, already well-known in human U-shape fibers were observed in both species, other shapes with more complex geometry such as 6 and J shapes were encountered. The localisation of the different bundle morphologies, putatively reflecting the brain gyrification process, was different between humans and chimpanzees using an isomap-based shape analysis approach. Ultimately, the analysis aims to uncover both commonalities and disparities in SWMBs between chimpanzees and humans, shedding light on the evolution and organization of these crucial neural structures.


Asunto(s)
Encéfalo , Pan troglodytes , Sustancia Blanca , Pan troglodytes/anatomía & histología , Animales , Humanos , Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Sustancia Blanca/anatomía & histología , Sustancia Blanca/diagnóstico por imagen , Imagen de Difusión Tensora , Vías Nerviosas/anatomía & histología , Masculino , Especificidad de la Especie , Femenino , Procesamiento de Imagen Asistido por Computador , Conectoma
4.
Neuroimage ; 296: 120665, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38848981

RESUMEN

The perspective of personalized medicine for brain disorders requires efficient learning models for anatomical neuroimaging-based prediction of clinical conditions. There is now a consensus on the benefit of deep learning (DL) in addressing many medical imaging tasks, such as image segmentation. However, for single-subject prediction problems, recent studies yielded contradictory results when comparing DL with Standard Machine Learning (SML) on top of classical feature extraction. Most existing comparative studies were limited in predicting phenotypes of little clinical interest, such as sex and age, and using a single dataset. Moreover, they conducted a limited analysis of the employed image pre-processing and feature selection strategies. This paper extensively compares DL and SML prediction capacity on five multi-site problems, including three increasingly complex clinical applications in psychiatry namely schizophrenia, bipolar disorder, and Autism Spectrum Disorder (ASD) diagnosis. To compensate for the relative scarcity of neuroimaging data on these clinical datasets, we also evaluate three pre-training strategies for transfer learning from brain imaging of the general healthy population: self-supervised learning, generative modeling and supervised learning with age. Overall, we find similar performance between randomly initialized DL and SML for the three clinical tasks and a similar scaling trend for sex prediction. This was replicated on an external dataset. We also show highly correlated discriminative brain regions between DL and linear ML models in all problems. Nonetheless, we demonstrate that self-supervised pre-training on large-scale healthy population imaging datasets (N≈10k), along with Deep Ensemble, allows DL to learn robust and transferable representations to smaller-scale clinical datasets (N≤1k). It largely outperforms SML on 2 out of 3 clinical tasks both in internal and external test sets. These findings suggest that the improvement of DL over SML in anatomical neuroimaging mainly comes from its capacity to learn meaningful and useful abstract representations of the brain anatomy, and it sheds light on the potential of transfer learning for personalized medicine in psychiatry.


Asunto(s)
Aprendizaje Profundo , Neuroimagen , Esquizofrenia , Humanos , Neuroimagen/métodos , Femenino , Esquizofrenia/diagnóstico por imagen , Masculino , Adulto , Encéfalo/diagnóstico por imagen , Aprendizaje Automático , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno Bipolar/diagnóstico por imagen , Persona de Mediana Edad , Adulto Joven , Psiquiatría/métodos
5.
Cereb Cortex ; 34(6)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38869374

RESUMEN

The central sulcus divides the primary motor and somatosensory cortices in many anthropoid primate brains. Differences exist in the surface area and depth of the central sulcus along the dorso-ventral plane in great apes and humans compared to other primate species. Within hominid species, there are variations in the depth and aspect of their hand motor area, or knob, within the precentral gyrus. In this study, we used post-image analyses on magnetic resonance images to characterize the central sulcus shape of humans, chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), and orangutans (Pongo pygmaeus and Pongo abelii). Using these data, we examined the morphological variability of central sulcus in hominids, focusing on the hand region, a significant change in human evolution. We show that the central sulcus shape differs between great ape species, but all show similar variations in the location of their hand knob. However, the prevalence of the knob location along the dorso-ventral plane and lateralization differs between species and the presence of a second ventral motor knob seems to be unique to humans. Humans and orangutans exhibit the most similar and complex central sulcus shapes. However, their similarities may reflect divergent evolutionary processes related to selection for different positional and habitual locomotor functions.


Asunto(s)
Evolución Biológica , Gorilla gorilla , Hominidae , Imagen por Resonancia Magnética , Corteza Motora , Pan troglodytes , Filogenia , Animales , Humanos , Masculino , Pan troglodytes/anatomía & histología , Pan troglodytes/fisiología , Gorilla gorilla/anatomía & histología , Gorilla gorilla/fisiología , Femenino , Corteza Motora/anatomía & histología , Corteza Motora/fisiología , Corteza Motora/diagnóstico por imagen , Hominidae/anatomía & histología , Hominidae/fisiología , Adulto , Mano/fisiología , Mano/anatomía & histología , Adulto Joven , Pongo pygmaeus/anatomía & histología , Pongo pygmaeus/fisiología , Especificidad de la Especie , Pongo abelii/anatomía & histología , Pongo abelii/fisiología
6.
Front Neurosci ; 18: 1396518, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38872943

RESUMEN

Diffusion Magnetic Resonance Imaging tractography is a non-invasive technique that produces a collection of streamlines representing the main white matter bundle trajectories. Methods, such as fiber clustering algorithms, are important in computational neuroscience and have been the basis of several white matter analysis methods and studies. Nevertheless, these clustering methods face the challenge of the absence of ground truth of white matter fibers, making their evaluation difficult. As an alternative solution, we present an innovative brain fiber bundle simulator that uses spline curves for fiber representation. The methodology uses a tubular model for the bundle simulation based on a bundle centroid and five radii along the bundle. The algorithm was tested by simulating 28 Deep White Matter atlas bundles, leading to low inter-bundle distances and high intersection percentages between the original and simulated bundles. To prove the utility of the simulator, we created three whole-brain datasets containing different numbers of fiber bundles to assess the quality performance of QuickBundles and Fast Fiber Clustering algorithms using five clustering metrics. Our results indicate that QuickBundles tends to split less and Fast Fiber Clustering tends to merge less, which is consistent with their expected behavior. The performance of both algorithms decreases when the number of bundles is increased due to higher bundle crossings. Additionally, the two algorithms exhibit robust behavior with input data permutation. To our knowledge, this is the first whole-brain fiber bundle simulator capable of assessing fiber clustering algorithms with realistic data.

7.
Front Neurosci ; 18: 1394681, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737100

RESUMEN

In recent years, there has been a growing interest in studying the Superficial White Matter (SWM). The SWM consists of short association fibers connecting near giry of the cortex, with a complex organization due to their close relationship with the cortical folding patterns. Therefore, their segmentation from dMRI tractography datasets requires dedicated methodologies to identify the main fiber bundle shape and deal with spurious fibers. This paper presents an enhanced short fiber bundle segmentation based on a SWM bundle atlas and the filtering of noisy fibers. The method was tuned and evaluated over HCP test-retest probabilistic tractography datasets (44 subjects). We propose four fiber bundle filters to remove spurious fibers. Furthermore, we include the identification of the main fiber fascicle to obtain well-defined fiber bundles. First, we identified four main bundle shapes in the SWM atlas, and performed a filter tuning in a subset of 28 subjects. The filter based on the Convex Hull provided the highest similarity between corresponding test-retest fiber bundles. Subsequently, we applied the best filter in the 16 remaining subjects for all atlas bundles, showing that filtered fiber bundles significantly improve test-retest reproducibility indices when removing between ten and twenty percent of the fibers. Additionally, we applied the bundle segmentation with and without filtering to the ABIDE-II database. The fiber bundle filtering allowed us to obtain a higher number of bundles with significant differences in fractional anisotropy, mean diffusivity, and radial diffusivity of Autism Spectrum Disorder patients relative to controls.

8.
Front Neurosci ; 18: 1333243, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38529266

RESUMEN

We present a Python library (Phybers) for analyzing brain tractography data. Tractography datasets contain streamlines (also called fibers) composed of 3D points representing the main white matter pathways. Several algorithms have been proposed to analyze this data, including clustering, segmentation, and visualization methods. The manipulation of tractography data is not straightforward due to the geometrical complexity of the streamlines, the file format, and the size of the datasets, which may contain millions of fibers. Hence, we collected and structured state-of-the-art methods for the analysis of tractography and packed them into a Python library, to integrate and share tools for tractography analysis. Due to the high computational requirements, the most demanding modules were implemented in C/C++. Available functions include brain Bundle Segmentation (FiberSeg), Hierarchical Fiber Clustering (HClust), Fast Fiber Clustering (FFClust), normalization to a reference coordinate system, fiber sampling, calculation of intersection between sets of brain fibers, tools for cluster filtering, calculation of measures from clusters, and fiber visualization. The library tools were structured into four principal modules: Segmentation, Clustering, Utils, and Visualization (Fibervis). Phybers is freely available on a GitHub repository under the GNU public license for non-commercial use and open-source development, which provides sample data and extensive documentation. In addition, the library can be easily installed on both Windows and Ubuntu operating systems through the pip library.

9.
Cereb Cortex ; 34(2)2024 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-38236742

RESUMEN

The segregation of the cortical mantle into cytoarchitectonic areas provides a structural basis for the specialization of different brain regions. In vivo neuroimaging experiments can be linked to this postmortem cytoarchitectonic parcellation via Julich-Brain. This atlas embeds probabilistic maps that account for inter-individual variability in the localization of cytoarchitectonic areas in the reference spaces targeted by spatial normalization. We built a framework to improve the alignment of architectural areas across brains using cortical folding landmarks. This framework, initially designed for in vivo imaging, was adapted to postmortem histological data. We applied this to the first 14 brains used to establish the Julich-Brain atlas to infer a refined atlas with more focal probabilistic maps. The improvement achieved is significant in the primary regions and some of the associative areas. This framework also provides a tool for exploring the relationship between cortical folding patterns and cytoarchitectonic areas in different cortical regions to establish new landmarks in the remainder of the cortex.


Asunto(s)
Encéfalo , Neuroimagen , Autopsia , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico/métodos
10.
J Anat ; 244(2): 274-296, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37935387

RESUMEN

Palaeoneurology is a complex field as the object of study, the brain, does not fossilize. Studies rely therefore on the (brain) endocranial cast (often named endocast), the only available and reliable proxy for brain shape, size and details of surface. However, researchers debate whether or not specific marks found on endocasts correspond reliably to particular sulci and/or gyri of the brain that were imprinted in the braincase. The aim of this study is to measure the accuracy of sulcal identification through an experiment that reproduces the conditions that palaeoneurologists face when working with hominin endocasts. We asked 14 experts to manually identify well-known foldings in a proxy endocast that was obtained from an MRI of an actual in vivo Homo sapiens head. We observe clear differences in the results when comparing the non-corrected labels (the original labels proposed by each expert) with the corrected labels. This result illustrates that trying to reconstruct a sulcus following the very general known shape/position in the literature or from a mean specimen may induce a bias when looking at an endocast and trying to follow the marks observed there. We also observe that the identification of sulci appears to be better in the lower part of the endocast compared to the upper part. The results concerning specific anatomical traits have implications for highly debated topics in palaeoanthropology. Endocranial description of fossil specimens should in the future consider the variation in position and shape of sulci in addition to using models of mean brain shape. Moreover, it is clear from this study that researchers can perceive sulcal imprints with reasonably high accuracy, but their correct identification and labelling remains a challenge, particularly when dealing with extinct species for which we lack direct knowledge of the brain.


Asunto(s)
Hominidae , Cráneo , Humanos , Animales , Cráneo/anatomía & histología , Encéfalo , Fósiles , Imagen por Resonancia Magnética , Evolución Biológica
11.
Neuroimage ; 282: 120362, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37722605

RESUMEN

Mapping the chimpanzee brain connectome and comparing it to that of humans is key to our understanding of similarities and differences in primate evolution that occurred after the split from their common ancestor around 6 million years ago. In contrast to studies on macaque species' brains, fewer studies have specifically addressed the structural connectivity of the chimpanzee brain and its comparison with the human brain. Most comparative studies in the literature focus on the anatomy of the cortex and deep nuclei to evaluate how their morphology and asymmetry differ from that of the human brain, and some studies have emerged concerning the study of brain connectivity among humans, monkeys, and apes. In this work, we established a new white matter atlas of the deep and superficial white matter structural connectivity in chimpanzees. In vivo anatomical and diffusion-weighted magnetic resonance imaging (MRI) data were collected on a 3-Tesla MRI system from 39 chimpanzees. These datasets were subsequently processed using a novel fiber clustering pipeline adapted to the chimpanzee brain, enabling us to create two novel deep and superficial white matter connectivity atlases representative of the chimpanzee brain. These atlases provide the scientific community with an important and novel set of reference data for understanding the commonalities and differences in structural connectivity between the human and chimpanzee brains. We believe this study to be innovative both in its novel approach and in mapping the superficial white matter bundles in the chimpanzee brain, which will contribute to a better understanding of hominin brain evolution.


Asunto(s)
Conectoma , Sustancia Blanca , Humanos , Animales , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/anatomía & histología , Pan troglodytes , Encéfalo/diagnóstico por imagen , Encéfalo/anatomía & histología , Imagen por Resonancia Magnética , Mapeo Encefálico , Macaca
12.
Alzheimers Dement ; 19(12): 5700-5718, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37422285

RESUMEN

INTRODUCTION: This study aims to examine whether physical activity moderates the association between biomarkers of brain pathologies and dementia risk. METHODS: From the Memento cohort, we analyzed 1044 patients with mild cognitive impairment, aged 60 and older. Self-reported physical activity was assessed using the International Physical Activity Questionnaire. Biomarkers of brain pathologies comprised medial temporal lobe atrophy (MTA), white matter lesions, and plasma amyloid beta (Aß)42/40 and phosphorylated tau181. Association between physical activity and risk of developing dementia over 5 years of follow-up, and interactions with biomarkers of brain pathologies were tested. RESULTS: Physical activity moderated the association between MTA and plasma Aß42/40 level and increased dementia risk. Compared to participants with low physical activity, associations of both MTA and plasma Aß42/40 on dementia risk were attenuated in participants with high physical activity. DISCUSSION: Although reverse causality cannot be excluded, this work suggests that physical activity may contribute to cognitive reserve. HIGHLIGHTS: Physical activity is an interesting modifiable target for dementia prevention. Physical activity may moderate the impact of brain pathology on dementia risk. Medial temporal lobe atrophy and plasma amyloid beta 42/40 ratio were associated with increased dementia risk especially in those with low level of physical activity.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Humanos , Persona de Mediana Edad , Anciano , Demencia/complicaciones , Péptidos beta-Amiloides , Imagen por Resonancia Magnética , Progresión de la Enfermedad , Disfunción Cognitiva/patología , Biomarcadores , Encéfalo/patología , Atrofia/patología , Enfermedad de Alzheimer/patología , Proteínas tau
13.
Neuroimage ; 276: 120212, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37269959

RESUMEN

Intrinsic coupling modes (ICMs) can be observed in ongoing brain activity at multiple spatial and temporal scales. Two families of ICMs can be distinguished: phase and envelope ICMs. The principles that shape these ICMs remain partly elusive, in particular their relation to the underlying brain structure. Here we explored structure-function relationships in the ferret brain between ICMs quantified from ongoing brain activity recorded with chronically implanted micro-ECoG arrays and structural connectivity (SC) obtained from high-resolution diffusion MRI tractography. Large-scale computational models were used to explore the ability to predict both types of ICMs. Importantly, all investigations were conducted with ICM measures that are sensitive or insensitive to volume conduction effects. The results show that both types of ICMs are significantly related to SC, except for phase ICMs when using measures removing zero-lag coupling. The correlation between SC and ICMs increases with increasing frequency which is accompanied by reduced delays. Computational models produced results that were highly dependent on the specific parameter settings. The most consistent predictions were derived from measures solely based on SC. Overall, the results demonstrate that patterns of cortical functional coupling as reflected in both phase and envelope ICMs are both related, albeit to different degrees, to the underlying structural connectivity in the cerebral cortex.


Asunto(s)
Corteza Cerebral , Hurones , Humanos , Animales , Corteza Cerebral/diagnóstico por imagen , Encéfalo , Mapeo Encefálico/métodos , Electrocorticografía
14.
Cereb Cortex ; 33(11): 6667-6680, 2023 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-36702802

RESUMEN

Brain folding patterns vary within the human species, but some folding properties are common across individuals, including the Sylvian fissure's inter-hemispheric asymmetry. Contrarily to the other brain folds (sulci), the Sylvian fissure develops through the process of opercularization, with the frontal, parietal, and temporal lobes growing over the insular lobe. Its asymmetry may be related to the leftward functional lateralization for language processing, but the time course of these asymmetries' development is still poorly understood. In this study, we investigated refined shape features of the Sylvian fissure and their longitudinal development in 71 infants born extremely preterm (mean gestational age at birth: 26.5 weeks) and imaged once before and once at term-equivalent age (TEA). We additionally assessed asymmetrical sulcal patterns at TEA in the perisylvian and inferior frontal regions, neighbor to the Sylvian fissure. While reproducing renowned strong asymmetries in the Sylvian fissure, we captured an early encoding of its main asymmetrical shape features, and we observed global asymmetrical shape features representative of a more pronounced opercularization in the left hemisphere, contrasting with the previously reported right hemisphere advance in sulcation around birth. This added novel insights about the processes governing early-life brain folding mechanisms, potentially linked to the development of language-related capacities.


Asunto(s)
Lateralidad Funcional , Recien Nacido Prematuro , Lactante , Humanos , Recién Nacido , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/anatomía & histología
15.
Neuroimage ; 265: 119773, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36442731

RESUMEN

The expansion of the cerebral cortex is one of the most distinctive changes in the evolution of the human brain. Cortical expansion and related increases in cortical folding may have contributed to emergence of our capacities for high-order cognitive abilities. Molecular analysis of humans, archaic hominins, and non-human primates has allowed identification of chromosomal regions showing evolutionary changes at different points of our phylogenetic history. In this study, we assessed the contributions of genomic annotations spanning 30 million years to human sulcal morphology measured via MRI in more than 18,000 participants from the UK Biobank. We found that variation within brain-expressed human gained enhancers, regulatory genetic elements that emerged since our last common ancestor with Old World monkeys, explained more trait heritability than expected for the left and right calloso-marginal posterior fissures and the right central sulcus. Intriguingly, these are sulci that have been previously linked to the evolution of locomotion in primates and later on bipedalism in our hominin ancestors.


Asunto(s)
Encéfalo , Corteza Cerebral , Animales , Humanos , Filogenia , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/anatomía & histología , Encéfalo/anatomía & histología , Primates , Imagen por Resonancia Magnética , Variación Genética , Elementos de Facilitación Genéticos/genética
16.
Alzheimers Dement ; 19(6): 2332-2342, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36464896

RESUMEN

INTRODUCTION: Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension-dementia association are still poorly understood. METHODS: We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data. RESULTS: Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers. DISCUSSION: These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension-dementia association. HIGHLIGHTS: Paths of hypertension-cognition association were assessed by structural equation models. The hypertension-cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension-cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Hipertensión , Humanos , Enfermedad de Alzheimer/metabolismo , Estudios Transversales , Tomografía de Emisión de Positrones , Imagen por Resonancia Magnética , Cognición/fisiología , Disfunción Cognitiva/metabolismo , Biomarcadores , Péptidos beta-Amiloides/metabolismo
18.
Neurology ; 100(5): e473-e484, 2023 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-36261295

RESUMEN

BACKGROUND AND OBJECTIVE: Blood biomarkers for Alzheimer disease (AD) have consistently proven to be associated with CSF or PET biomarkers and effectively discriminate AD from other neurodegenerative diseases. Our aim was to test their utility in clinical practice, from a multicentric unselected prospective cohort where patients presented with a large spectrum of cognitive deficits or complaints. METHODS: The MEMENTO cohort enrolled 2,323 outpatients with subjective cognitive complaint (SCC) or mild cognitive impairment (MCI) consulting in 26 French memory clinics. Participants had neuropsychological assessments, MRI, and blood sampling at baseline. CSF sampling and amyloid PET were optional. Baseline blood Aß42/40 ratio, total tau, p181-tau, and neurofilament light chain (NfL) were measured using a Simoa HD-X analyzer. An expert committee validated incident dementia cases during a 5-year follow-up period. RESULTS: Overall, 2,277 individuals had at least 1 baseline blood biomarker available (n = 357 for CSF subsample, n = 649 for PET subsample), among whom 257 were diagnosed with clinical AD/mixed dementia during follow-up. All blood biomarkers but total tau were mildly correlated with their equivalence in the CSF (r = 0.33 to 0.46, p < 0.0001) and were associated with amyloid-PET status (p < 0.0001). Blood p181-tau was the best blood biomarker to identify amyloid-PET positivity (area under the curve = 0.74 [95% CI = 0.69; 0.79]). Higher blood and CSF p181-tau and NfL concentrations were associated with accelerated time to AD dementia onset with similar incidence rates, whereas blood Aß42/40 was less efficient than CSF Aß42/40. Blood p181-tau alone was the best blood predictor of 5-year AD/mixed dementia risk (c-index = 0.73 [95% CI = 0.69; 0.77]); its accuracy was higher in patients with clinical dementia rating (CDR) = 0 (c-index = 0.83 [95% CI = 0.69; 0.97]) than in patients with CDR = 0.5 (c-index = 0.70 [95% CI = 0.66; 0.74]). A "clinical" reference model (combining demographics and neuropsychological assessment) predicted AD/mixed dementia risk with a c-index = 0.88 [95% CI = 0.86-0.91] and performance increased to 0.90 [95% CI = 0.88; 0.92] when adding blood p181-tau + Aß42/40. A "research" reference model (clinical model + apolipoprotein E genotype and AD signature on MRI) had a c-index = 0.91 [95% CI = 0.89-0.93] increasing to 0.92 [95% CI = 0.90; 0.93] when adding blood p181-tau + Aß42/40. Chronic kidney disease and vascular comorbidities did not affect predictive performances. DISCUSSION: In a clinic-based cohort of patients with SCC or MCI, blood biomarkers may be good hallmarks of underlying pathology but add little to 5-year dementia risk prediction models including traditional predictors.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Demencias Mixtas , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Estudios Prospectivos , Péptidos beta-Amiloides , Proteínas tau , Biomarcadores , Disfunción Cognitiva/diagnóstico por imagen , Fragmentos de Péptidos
19.
Cereb Cortex ; 33(5): 1925-1940, 2023 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-35697647

RESUMEN

The superior temporal sulcus (STS) is a conserved fold that divides the middle and superior temporal gyri. In humans, there is considerable variation in the shape, folding pattern, lateralization, and depth of the STS that have been reported to be associated with social cognition and linguistic functions. We examined the role that genetic factors play on individual variation in STS morphology in chimpanzees. The surface area and depth of the STS were quantified in sample of 292 captive chimpanzees comprised of two genetically isolated population of individuals. The chimpanzees had been previously genotyped for AVPR1A and KIAA0319, two genes that play a role in social cognition and communication in humans. Single nucleotide polymorphisms in the KIAA0319 and AVPR1A genes were associated with average depth as well as asymmetries in the STS. By contrast, we found no significant effects of these KIA0319 and AVPR1A polymorphism on surface area and depth measures for the central sulcus. The overall findings indicate that genetic factors account for a small to moderate amount of variation in STS morphology in chimpanzees. These findings are discussed in the context of the role of the STS in social cognition and language in humans and their potential evolutionary origins.


Asunto(s)
Pan troglodytes , Polimorfismo de Nucleótido Simple , Animales , Humanos , Pan troglodytes/genética , Genotipo , Alelos , Lóbulo Temporal
20.
J Sport Health Sci ; 12(3): 324-332, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-33545345

RESUMEN

BACKGROUND: Age-related changes in brain structure may constitute the starting point for cerebral function alteration. Physical activity (PA) demonstrated favorable associations with total brain volume, but its relationship with cortical thickness (CT) remains unclear. We investigated the cross-sectional associations between PA level and CT in community-dwelling people aged 70 years and older. METHODS: A total of 403 older adults aged 74.8 ± 4.0 years (mean ± SD) who underwent a baseline magnetic resonance imaging examination and who had data on PA and confounders were included. PA was assessed with a questionnaire. Participants were categorized according to PA levels. Multiple linear regressions were used to compare the brain CT (mm) of the inactive group (no PA at all) with 6 active groups (growing PA levels) in 34 regions of interest. RESULTS: Compared with inactive persons, people who achieved PA at a level of 1500-1999 metabolic equivalent task-min/week (i.e., about 6-7 h of brisk walking for exercise and those who achieved it at 2000-2999 metabolic equivalent task-min/week (i.e., 8-11 h of brisk walking for exercise) had higher CT in the fusiform gyrus and the temporal pole. Additionally, dose-response associations between PA and CT were found in the fusiform gyrus (B = 0.011, SE = 0.004, adj. p = 0.035), the temporal pole (B = 0.026, SE = 0.009, adj. p = 0.048), and the caudal middle frontal gyrus, the entorhinal, medial orbitofrontal, lateral occipital, and insular cortices. CONCLUSION: This study demonstrates a positive association between PA level and CT in temporal areas such as the fusiform gyrus, a brain region often associated to Alzheimer's disease in people aged 70 years and older. Future investigations focusing on PA type may help to fulfil remaining knowledge gaps in this field.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Anciano , Anciano de 80 o más Años , Estudios Transversales , Ejercicio Físico , Encéfalo , Caminata
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