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The functional organization of the frontal lobe is a source of debate, focusing on broad functional subdivisions, large-scale networks, or local refined specificities. Multiple neurocognitive models have tried to explain how functional interactions between cingulate and lateral frontal regions contribute to decision making and cognitive control, but their neuroanatomical bases remain unclear. We provide a detailed description of the functional connectivity between cingulate and lateral frontal regions using resting-state functional MRI in rhesus macaques. The analysis focuses on the functional connectivity of the rostral part of the cingulate sulcus with the lateral frontal cortex. Data-driven and seed-based analysis revealed three clusters within the cingulate sulcus organized along the rostro-caudal axis: the anterior, mid, and posterior clusters display increased functional connectivity with, respectively, the anterior lateral prefrontal regions, face-eye lateral frontal motor cortical areas, and hand lateral frontal motor cortex. The location of these clusters can be predicted in individual subjects based on morphological landmarks. These results suggest that the anterior cluster corresponds to the anterior cingulate cortex, whereas the posterior clusters correspond to the face-eye and hand cingulate motor areas within the anterior midcingulate cortex. These data provide a comprehensive framework to identify cingulate subregions based on functional connectivity and local organization.
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Mapeo Encefálico , Giro del Cíngulo , Macaca mulatta , Imagen por Resonancia Magnética , Vías Nerviosas , Giro del Cíngulo/fisiología , Giro del Cíngulo/diagnóstico por imagen , Animales , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico/métodos , Masculino , Vías Nerviosas/fisiología , Vías Nerviosas/diagnóstico por imagen , Lóbulo Frontal/fisiología , Lóbulo Frontal/diagnóstico por imagen , FemeninoRESUMEN
OBJECTIVES: Integration reflects the level of coordinated variation of the phenotype. The integration of postcranial elements can be studied from a functional perspective, especially with regards to locomotion. This study investigates the link between locomotion, femoral structural properties, and femur-pelvis complex morphology. MATERIALS AND METHODS: We measured (1) morphological integration between femoral and pelvic morphologies using geometric morphometrics, and (2) covariation between femoral/pelvic morphologies and femoral diaphyseal cross-sectional properties, which we defined as morpho-structural integration. Morphological and morpho-structural integration patterns were measured among humans (n = 19), chimpanzees and bonobos (n = 16), and baboons (n = 14), whose locomotion are distinct. RESULTS: Baboons show the highest magnitude of morphological integration and the lowest of morpho-structural integration. Chimpanzees and bonobos show intermediate magnitude of morphological and morpho-structural integration. Yet, body size seems to have a considerable influence on both integration patterns, limiting the interpretations. Finally, humans present the lowest morphological integration and the highest morpho-structural integration between femoral morphology and structural properties but not between pelvic morphology and femur. DISCUSSION: Morphological and morpho-structural integration depict distinct strategies among the samples. A strong morphological integration among baboon's femur-pelvis module might highlight evidence for long-term adaptation to quadrupedalism. In humans, it is likely that distinct selective pressures associated with the respective function of the pelvis and the femur tend to decrease morphological integration. Conversely, high mechanical loading on the hindlimbs during bipedal locomotion might result in specific combination of structural and morphological features within the femur.
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Fémur , Locomoción , Animales , Fémur/anatomía & histología , Fémur/fisiología , Femenino , Masculino , Humanos , Locomoción/fisiología , Pelvis/anatomía & histología , Pelvis/fisiología , Pan paniscus/fisiología , Pan paniscus/anatomía & histología , Pan troglodytes/anatomía & histología , Pan troglodytes/fisiología , Antropología Física , Huesos Pélvicos/anatomía & histología , Huesos Pélvicos/fisiología , Adulto , Papio/fisiología , Papio/anatomía & histologíaRESUMEN
Over the course of evolution, the amygdala (AMG) and medial frontal cortex (mPFC) network, involved in behavioral adaptation, underwent structural changes in the old-world monkey and human lineages. Yet, whether and how the functional organization of this network differs remains poorly understood. Using resting-state functional magnetic resonance imagery, we show that the functional connectivity (FC) between AMG nuclei and mPFC regions differs between humans and awake macaques. In humans, the AMG-mPFC FC displays U-shaped pattern along the corpus callosum: a positive FC with the ventromedial prefrontal (vmPFC) and anterior cingulate cortex (ACC), a negative FC with the anterior mid-cingulate cortex (MCC), and a positive FC with the posterior MCC. Conversely, in macaques, the negative FC shifted more ventrally at the junction between the vmPFC and the ACC. The functional organization divergence of AMG-mPFC network between humans and macaques might help understanding behavioral adaptation abilities differences in their respective socio-ecological niches.
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Macaca , Corteza Prefrontal , Humanos , Animales , Corteza Prefrontal/diagnóstico por imagen , Amígdala del Cerebelo/diagnóstico por imagen , Lóbulo Frontal , Corteza CerebralRESUMEN
Our ability to understand how to interact with familiar objects is supported by conceptual tool knowledge. Conceptual tool knowledge includes action tool and semantic tool knowledge which are supported by the ventro-dorsal and the ventral pathways, respectively. This apparent functional segregation has been recently called into question. In a block-design fMRI study, 35 participants were asked to complete manipulation, function, and association judgment tasks about pairs of familiar objects. Our results showed that lateral occipitotemporal cortex in the ventral pathway was more sensitive to manipulation and function judgment tasks compared with association judgment tasks. Functional connectivity analyses revealed distinct coupling patterns between inferior parietal lobule, lateral occipitotemporal cortex, and fusiform gyrus. Taken together, these data indicate that action tool and semantic tool knowledge are both supported by ventral and ventro-dorsal pathways. Moreover, the explicit retrieval of these representations is supported by the functional coupling of common and distinct brain regions of the posterior tool processing network varying according to the kind of relations to be retrieved.
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Mapeo Encefálico , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico/métodos , Semántica , Corteza Cerebral/diagnóstico por imagen , Encéfalo/diagnóstico por imagenRESUMEN
Most recent research highlights how a specific form of causal understanding, namely technical reasoning, may support the increasing complexity of tools and techniques developed by humans over generations, i.e., the cumulative technological culture (CTC). Thus, investigating the neurocognitive foundations of technical reasoning is essential to comprehend the emergence of CTC in our lineage. Whereas functional neuroimaging evidence started to highlight the critical role of the area PF of the left inferior parietal cortex (IPC) in technical reasoning, no studies explored the links between the structural characteristics of such a brain region and technical reasoning skills. Therefore, in this study, we assessed participants' technical-reasoning performance by using two ad-hoc psycho-technical tests; then, we extracted from participants' 3 T T1-weighted magnetic-resonance brain images the cortical thickness (i.e., a volume-related measure which is associated with cognitive performance as reflecting the size, density, and arrangement of cells in a brain region) of all the IPC regions for both hemispheres. We found that the cortical thickness of the left area PF predicts participants' technical-reasoning performance. Crucially, we reported no correlations between technical reasoning and the other IPC regions, possibly suggesting the specificity of the left area PF in generating technical knowledge. We discuss these findings from an evolutionary perspective, by speculating about how the evolution of parietal lobes may have supported the emergence of technical reasoning in our lineage.
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Lóbulo Parietal , Solución de Problemas , Encéfalo , Humanos , Lóbulo Parietal/diagnóstico por imagen , Tecnología , PensamientoRESUMEN
Atherosclerosis is a chronic systemic inflammatory disease, inducing cardiovascular and cerebrovascular acute events. A role of neuroinflammation is suspected, but not yet investigated in the gyrencephalic brain and the related activity at blood-brain interfaces is unknown. A non-human primate model of advanced atherosclerosis was first established using longitudinal blood samples, multimodal imaging and gene analysis in aged animals. Non-human primate carotid lesions were compared with human carotid endarterectomy samples. During the whole-body imaging session, imaging of neuroinflammation and choroid plexus function was performed. Advanced plaques were present in multiple sites, premature deaths occurred and downstream lesions (myocardial fibrosis, lacunar stroke) were present in this model. Vascular lesions were similar to in humans: high plaque activity on PET and MRI imaging and systemic inflammation (high plasma C-reactive protein levels: 42 ± 14 µg/ml). We also found the same gene association (metabolic, inflammatory and anti-inflammatory markers) as in patients with similar histological features. Metabolic imaging localized abnormal brain glucose metabolism in the frontal cortex. It corresponded to cortical neuro-inflammation (PET imaging) that correlated with C-reactive protein level. Multimodal imaging also revealed pronounced choroid plexus function impairment in aging atherosclerotic non-human primates. In conclusion, multimodal whole-body inflammation exploration at the vascular level and blood-brain interfaces identified high-risk aging atherosclerosis. These results open the way for systemic and central inflammation targeting in atherosclerosis in the new era of immunotherapy.
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In the primate brain, a set of areas in the ventrolateral frontal (VLF) cortex and the dorsomedial frontal (DMF) cortex appear to control vocalizations. The basic role of this network in the human brain and how it may have evolved to enable complex speech remain unknown. In the present functional neuroimaging study of the human brain, a multidomain protocol was utilized to investigate the roles of the various areas that comprise the VLF-DMF network in learning rule-based cognitive selections between different types of motor actions: manual, orofacial, nonspeech vocal, and speech vocal actions. Ventrolateral area 44 (a key component of the Broca's language production region in the human brain) is involved in the cognitive selection of orofacial, as well as, speech and nonspeech vocal responses; and the midcingulate cortex is involved in the analysis of speech and nonspeech vocal feedback driving adaptation of these responses. By contrast, the cognitive selection of speech vocal information requires this former network and the additional recruitment of area 45 and the presupplementary motor area. We propose that the basic function expressed by the VLF-DMF network is to exert cognitive control of orofacial and vocal acts and, in the language dominant hemisphere of the human brain, has been adapted to serve higher speech function. These results pave the way to understand the potential changes that could have occurred in this network across primate evolution to enable speech production.
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Cognición/fisiología , Lóbulo Frontal/fisiología , Corteza Motora/fisiología , Pliegues Vocales/fisiología , Voz/fisiología , Adulto , Animales , Evolución Biológica , Encéfalo , Mapeo Encefálico , Área de Broca , Femenino , Humanos , Lenguaje , Aprendizaje , Masculino , Red Nerviosa , Primates , Habla/fisiología , Vocalización Animal/fisiología , Adulto JovenRESUMEN
Sensory hypersensitivity is frequently encountered in autism spectrum disorder (ASD). Gamma-aminobutyric acid (GABA) has been hypothesized to play a role in tactile hypersensitivity. The aim of the present study was twofold. First, as a study showed that children with ASD have decreased GABA concentrations in the sensorimotor cortex, we aimed at determining whether the GABA reduction remained in adults with ASD. For this purpose, we used magnetic resonance spectroscopy to measure GABA concentration in the sensorimotor cortex of neurotypical adults (n = 19) and ASD adults (n = 18). Second, we aimed at characterizing correlations between GABA concentration and tactile hypersensitivity in ASD. GABA concentration in the sensorimotor cortex of adults with ASD was lower than in neurotypical adults (decrease by 17%). Interestingly, GABA concentrations were positively correlated with self-reported tactile hypersensitivity in adults with ASD (r = 0.50, P = 0.01), but not in neurotypical adults. In addition, GABA concentrations were negatively correlated with the intra-individual variation during threshold measurement, both in neurotypical adults (r = -0.47, P = 0.04) and in adults with ASD (r = -0.59, P = 0.01). In other words, in both groups, the higher the GABA level, the more precise the tactile sensation. These results highlight the key role of GABA in tactile sensitivity, and suggest that atypical GABA modulation contributes to tactile hypersensitivity in ASD. We discuss the hypothesis that hypersensitivity in ASD could be due to suboptimal predictions about sensations. Autism Research 2019, 12: 562-575. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism spectrum disorder (ASD) often experience tactile hypersensitivity. Here, our goal was to highlight a link between tactile hypersensitivity and the concentration of gamma-aminobutyric acid (GABA) (an inhibitory neurotransmitter) in the brain of adults with ASD. Indeed, self-reported hypersensitivity correlated with reduced GABA levels in brain areas processing touch. Our study suggests that this neurotransmitter may play a key role in tactile hypersensitivity in autism.
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Trastorno del Espectro Autista/fisiopatología , Corteza Sensoriomotora/metabolismo , Percepción del Tacto/fisiología , Ácido gamma-Aminobutírico/metabolismo , Adulto , Femenino , Humanos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Corteza Sensoriomotora/diagnóstico por imagen , Corteza Sensoriomotora/fisiopatologíaRESUMEN
Diffusion Magnetic Resonance Imaging (dMRI) has been widely used to investigate human brain microstructure and connectivity and its abnormalities in a variety of brain deficits, whether acute, neurodevelopmental or neurodegenerative. However, the biological interpretation and validation of dMRI data modelling is still a crucial challenge in the field. In this respect, achieving high spatial resolution in-vivo dMRI in the non-human primate to compare these observations both with human dMRI on the one hand and 'ground truth' microstructural and histological data on the other hand is of outmost importance. Here, we developed a dMRI pulse sequence based on 3D-multishot Echo Planar Imaging (3D-msEPI) on a 3T human clinical scanner. We demonstrate the feasibility of cerebral dMRI at an isotropic resolution of 0.5 mm in 4 anesthetized macaque monkeys. The added value of the high-resolution dMRI is illustrated by focusing on two aspects. First, we show an enhanced descriptive power of the fine substructure of the hippocampus. Second, we show a more physiological description of the interface between cortex grey matter, superficial and deep white matter. Overall, the high spatial resolution dMRI acquisition method proposed in this study is a significant achievement with respect to the state of the art of dMRI on anesthetized monkeys. This study highlights also the potential of very high-resolution dMRI to precisely capture the microstructure of thin cerebral structures such as the hippocampus and superficial white matter.
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Imagen de Difusión Tensora/métodos , Imagen Eco-Planar/métodos , Hipocampo/anatomía & histología , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Macaca mulatta/anatomía & histología , Sustancia Blanca/anatomía & histología , Anestesia , Animales , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Masculino , Sustancia Blanca/diagnóstico por imagenRESUMEN
In this article, we report the safety evaluation of gadolinium-based nanoparticles in nonhuman primates (NHP) in the context of magnetic resonance imaging (MRI) studies in atherosclerosis bearing animals and healthy controls. In healthy NHP, the pharmacokinetics and toxicity profiles demonstrated the absence of dose, time, and sex-effects, as well as a suitable tolerance of intravenous administration of the nanoparticles. We investigated their imaging properties for arterial plaque imaging in a standard diet or a high cholesterol diet NHP, and compared their characteristics with clinically applied Gd-chelate. This preliminary investigation reports the efficient and safe imaging of atherosclerotic plaques.
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Aterosclerosis/diagnóstico por imagen , Medios de Contraste/efectos adversos , Dieta Alta en Grasa/efectos adversos , Gadolinio/efectos adversos , Administración Intravenosa , Animales , Aterosclerosis/inducido químicamente , Aterosclerosis/veterinaria , Medios de Contraste/farmacocinética , Femenino , Gadolinio/farmacocinética , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética/veterinaria , Masculino , Nanopartículas/química , PrimatesRESUMEN
BACKGROUND: Subjective cognitive decline (SCD) may be the first clinical sign of Alzheimer's disease (AD). SCD individuals with normal cognition may already have significant hippocampal atrophy, a well-known feature of AD. OBJECTIVE: To test the hypothesis that SCD, compared to healthy individuals without SCD, have a pattern of hippocampal subfield atrophy similar to that measured in the AD pathology. METHODS: 17 SCD, 21 AD, and 40 matched controls underwent a standard T1-weighted MRI and a dedicated high-resolution MRI proton-density hippocampal sequence. For each participant, three hippocampal regions-of-interest were manually delineated on the proton-density hippocampal sequence corresponding to the CA1, subiculum, and other (including CA2-3-4 and dentate gyrus) subfields. Total intracranial volume (TIV)-normalized subfield volumes were compared between-group. Voxelwise group comparisons assessed from the standard T1 MRI were also projected on 3D hippocampal surface views. RESULTS: Both patient groups showed significant TIV-normalized volume decrease in hippocampus global volume and in CA1 and subiculum subfields as well as in the other subfield in AD compared to controls. Significant differences were observed between SCD and AD in hippocampus global TIV-normalized volume. Atrophy maps on hippocampal surface showed major involvement of the lateral part (CA1) in both SCD and AD, with larger overlap of other regions in AD. CONCLUSION: The findings indicate topographically similar hippocampal subfield changes in SCD individuals as those found in AD. This further highlights the relevance of SCD recruited from a memory clinic in assessing pre-dementia AD stages.
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Trastornos del Conocimiento/patología , Trastornos del Conocimiento/psicología , Hipocampo/patología , Imagenología Tridimensional , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Análisis de Varianza , Mapeo Encefálico , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , ProtonesRESUMEN
Magnetic resonance imaging (MRI) applied to the hippocampus is challenging in studies of the neurophysiology of memory and the physiopathology of numerous diseases such as epilepsy, Alzheimer's disease, ischemia, and depression. The hippocampus is a well-delineated cerebral structure with a multi-layered organization. Imaging of hippocampus layers is limited to a few studies and requires high magnetic field and gradient strength. We performed one conventional MRI sequence on a 7T MRI in order to visualize and to delineate the multi-layered hippocampal structure ex vivo in rat brains. We optimized a volumic three-dimensional T2 Rapid Acquisition Relaxation Enhancement (RARE) sequence and quantified the volume of the hippocampus and one of its thinnest layers, the stratum granulare of the dentate gyrus. Additionally, we tested passive staining by gadolinium with the aim of decreasing the acquisition time and increasing image contrast. Using appropriated settings, six discrete layers were differentiated within the hippocampus in rats. In the hippocampus proper or Ammon's Horn (AH): the stratum oriens, the stratum pyramidale of, the stratum radiatum, and the stratum lacunosum moleculare of the CA1 were differentiated. In the dentate gyrus: the stratum moleculare and the stratum granulare layer were seen distinctly. Passive staining of one brain with gadolinium decreased the acquisition time by four and improved the differentiation between the layers. A conventional sequence optimized on a 7T MRI with a standard receiver surface coil will allow us to study structural layers (signal and volume) of hippocampus in various rat models of neuropathology (anxiety, epilepsia, neurodegeneration).
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Hipocampo/anatomía & histología , Imagen por Resonancia Magnética/métodos , Animales , Medios de Contraste , Gadolinio , Imagenología Tridimensional/métodos , RatasRESUMEN
The E4 allele of the ApoE gene has consistently been shown to be related to an increased risk of Alzheimer's disease (AD). The E4 allele is also associated with functional and structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess volumes of deep grey matter structures of 22 healthy younger ApoE4 carriers and 22 non-carriers (20-38 years). Volumes of the nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen, thalamus and brain stem were calculated by FMRIB's Integrated Registration and Segmentation Tool (FIRST) algorithm. A significant drop in volume was found in the right hippocampus of ApoE4 carriers (ApoE4+) relative to non-carriers (ApoE4-), while there was a borderline significant decrease in the volume of the left hippocampus of ApoE4 carriers. The volumes of no other structures were found to be significantly affected by genotype. Atrophy has been found to be a sensitive marker of neurodegenerative changes, and our results show that within a healthy young population, the presence of the ApoE4+ carrier gene leads to volume reduction in a structure that is vitally important for memory formation. Our results suggest that the hippocampus may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age. Although volume reductions were noted bilaterally in the hippocampus, atrophy was more pronounced in the right hippocampus. This finding relates to previous work which has noted a compensatory increase in right hemisphere activity in ApoE4 carriers in response to preclinical declines in memory function. Possession of the ApoE4 allele may lead to greater predilection for right hemisphere atrophy even in healthy young subjects in their twenties.
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Apolipoproteína E4/genética , Heterocigoto , Hipocampo/patología , Imagen por Resonancia Magnética , Adulto , Atrofia , Encéfalo/crecimiento & desarrollo , Femenino , Hipocampo/crecimiento & desarrollo , Humanos , Masculino , Tamaño de los Órganos , Adulto JovenRESUMEN
Previous PET and MRI studies have indicated that the degree to which pathology translates into clinical symptoms is strongly dependent on sex with women more likely to express pathology as a diagnosis of AD, whereas men are more resistant to clinical symptoms in the face of the same degree of pathology. Here we use DTI to investigate the difference between male and female white matter tracts in healthy older participants (24 women, 16 men) and participants with mild cognitive impairment (21 women, 12 men). Differences between control and MCI participants were found in fractional anisotropy (FA), radial diffusion (DR), axial diffusion (DA) and mean diffusion (MD). A significant main effect of sex was also reported for FA, MD and DR indices, with male control and male MCI participants having significantly more microstructural damage than their female counterparts. There was no sex by diagnosis interaction. Male MCIs also had significantly less normalised grey matter (GM) volume than female MCIs. However, in terms of absolute brain volume, male controls had significantly more brain volume than female controls. Normalised GM and WM volumes were found to decrease significantly with age with no age by sex interaction. Overall, these data suggest that the same degree of cognitive impairment is associated with greater structural damage in men compared with women.
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Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Imagen por Resonancia Magnética , Caracteres Sexuales , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Radiografía , Factores SexualesRESUMEN
The apolipoprotein E4 (ApoE4) is an established risk factor for Alzheimer's disease (AD). Previous work has shown that this allele is associated with functional (fMRI) changes as well structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess the diffusion characteristics and the white matter (WM) tracts of healthy young (20-38 years) ApoE4 carriers and non-carriers. No significant differences in diffusion indices were found between young carriers (ApoE4+) and non-carriers (ApoE4-). There were also no significant differences between the groups in terms of normalised GM or WM volume. A feature selection algorithm (ReliefF) was used to select the most salient voxels from the diffusion data for subsequent classification with support vector machines (SVMs). SVMs were capable of classifying ApoE4 carrier and non-carrier groups with an extremely high level of accuracy. The top 500 voxels selected by ReliefF were then used as seeds for tractography which identified a WM network that included regions of the parietal lobe, the cingulum bundle and the dorsolateral frontal lobe. There was a non-significant decrease in volume of this WM network in the ApoE4 carrier group. Our results indicate that there are subtle WM differences between healthy young ApoE4 carriers and non-carriers and that the WM network identified may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age.
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Apolipoproteína E4/genética , Encéfalo/patología , Imagen de Difusión Tensora/métodos , Salud , Heterocigoto , Máquina de Vectores de Soporte , Adulto , Cognición , Demografía , Difusión , Femenino , Humanos , Masculino , Tamaño de los Órganos/genética , Adulto JovenRESUMEN
Few studies have looked at the potential of using diffusion tensor imaging (DTI) in conjunction with machine learning algorithms in order to automate the classification of healthy older subjects and subjects with mild cognitive impairment (MCI). Here we apply DTI to 40 healthy older subjects and 33 MCI subjects in order to derive values for multiple indices of diffusion within the white matter voxels of each subject. DTI measures were then used together with support vector machines (SVMs) to classify control and MCI subjects. Greater than 90% sensitivity and specificity was achieved using this method, demonstrating the potential of a joint DTI and SVM pipeline for fast, objective classification of healthy older and MCI subjects. Such tools may be useful for large scale drug trials in Alzheimer's disease where the early identification of subjects with MCI is critical.
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Trastornos del Conocimiento/diagnóstico , Disfunción Cognitiva/diagnóstico , Diagnóstico por Computador/métodos , Imagen de Difusión Tensora/métodos , Procesamiento de Señales Asistido por Computador , Anciano , Algoritmos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/patología , Automatización , Trastornos del Conocimiento/patología , Disfunción Cognitiva/patología , Difusión , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Máquina de Vectores de SoporteRESUMEN
Although there are numerous 3T MRI research devices all over the world, only a few functional studies at 3T have been done in anesthetized monkeys. In the past, anesthetized preparations were reported to be misleading when exploring cortical brain regions outside the primary sensory areas. Nonetheless, a great improvement has been achieved in the limited effect of anesthetic agents on the reactivity of the brain. Here, we re-address the feasibility and potential applications of the brain oxygen level dependent (BOLD) fMRI signal in Macaca mulatta monkeys that have been lightly anesthetized with sevoflurane and curarized. The monkeys were studied with commercially available coils and sequences using a 3T clinical magnet. We obtained sagittal T1 scout images, gray matter double inversion recovery, standard gradient echo sequences and gradient echo functional imaging sequences. Given that fMRI signals are most readily identified in the cerebral cortices, we optimized Echo Planar Imaging sequences to reproduce significant changes in the BOLD signal subsequent to a visual stimulation paradigm. Our results provide a satisfactory signal to noise ratio with a limited standard deviation range, when compared with studies on alert macaques. We suggest that the 3T magnet remains a valuable tool to analyze neural pathways in the macaque brain under light anesthesia and report the use of spatially resolved fMRI in higher visual areas of anesthetized monkeys. This methodology avoids the need for time-consuming training of awake monkeys, is stable over many hours, provides reproducible data and could be applied successfully to future functional studies.
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Anestesia , Imagen por Resonancia Magnética/métodos , Anestésicos por Inhalación , Animales , Atracurio , Imagen Eco-Planar , Estudios de Factibilidad , Procesamiento de Imagen Asistido por Computador , Macaca mulatta , Imagen por Resonancia Magnética/instrumentación , Masculino , Éteres Metílicos , Fármacos Neuromusculares no Despolarizantes , Oxígeno/sangre , Estimulación Luminosa , Reproducibilidad de los Resultados , Sevoflurano , Relación Señal-Ruido , Técnicas Estereotáxicas , Corteza Visual/anatomía & histología , Corteza Visual/fisiologíaRESUMEN
The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa.
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Enfermedad de Alzheimer/patología , Disfunción Cognitiva/patología , Anciano , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Jean Piaget's theory is a central reference point in the study of logico-mathematical development in children. One of the most famous Piagetian tasks is number conservation. Failures and successes in this task reveal two fundamental stages in children's thinking and judgment, shifting at approximately 7 years of age from visuospatial intuition to number conservation. In the current study, preschool children (nonconservers, 5-6 years of age) and school-age children (conservers, 9-10 years of age) were presented with Piaget's conservation-of-number task and monitored by functional magnetic resonance imaging (fMRI). The cognitive change allowing children to access conservation was shown to be related to the neural contribution of a bilateral parietofrontal network involved in numerical and executive functions. These fMRI results highlight how the behavioral and cognitive stages Piaget formulated during the 20th century manifest in the brain with age.
Asunto(s)
Desarrollo Infantil , Cognición , Función Ejecutiva , Imagen por Resonancia Magnética , Matemática , Psicología Infantil , Factores de Edad , Niño , Preescolar , Femenino , Lóbulo Frontal/fisiología , Humanos , Juicio , Masculino , Modelos Psicológicos , Pruebas Neuropsicológicas , Lóbulo Parietal/fisiología , PensamientoRESUMEN
White matter (WM) degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI) may be a key indicator of early damage in AD. Here, we analyzed WM diffusion tensor data using Tract-Based Spatial Statistics in conjunction with mixed-effects models. Four indices of diffusion were assessed in 61 healthy control, 19 non-amnestic MCIs, 14 amnestic MCIs, and 9 AD patients. The aim of the study was to use advanced mixed-effects models to investigate the retrogenesis hypothesis of AD, which suggests that tracts that are late to myelinate in ontogenetic development are the earliest to be affected in AD. Our results show that a number of late-myelinating pathways, including the parahippocampal region and the inferior longitudinal fasciculus, were predominantly affected by changes in WM volume. Conversely, early-myelinating pathways were found to be affected by a combination of both WM and gray matter (GM) atrophy. A model of the entire WM structure of the brain returned GM models for two indices of diffusion, suggesting that more complex regional landscapes of diffusion lie hidden beneath a global analysis of the entire brain. Our results warn against an explanation of white matter damage that points simply to one of two mechanisms: secondary degeneration or direct damage of myelin. We suggest that tracts may be affected by both mechanisms, with the balance depending on whether tracts are early or late-myelinating. A greater understanding of the pattern of WM changes in AD may prove useful for the early detection of AD.