RESUMEN
Alzheimer's disease (AD) is characterized by significant cerebral dysfunction, including increased amyloid deposition, gray matter atrophy, and changes in brain function. The involvement of highly connected network hubs, known as the "rich club," in the pathology of the disease remains inconclusive despite previous research efforts. In this study, we aimed to systematically assess the link between the rich club and AD using a multimodal neuroimaging approach. We employed network analyses of diffusion magnetic resonance imaging (MRI), longitudinal assessments of gray matter atrophy, amyloid deposition measurements using positron emission tomography (PET) imaging, and meta-analytic data on functional activation differences. Our study focused on evaluating the role of both the structural brain network's core and extended rich club regions in individuals with mild cognitive impairment (MCI) and those diagnosed with AD. Our findings revealed that structural rich club regions exhibited accelerated gray matter atrophy and increased amyloid deposition in both MCI and AD. Importantly, these regions remained unaffected by altered functional activation patterns observed outside the core rich club regions. These results shed light on the connection between two major AD biomarkers and the rich club, providing valuable insights into AD as a potential disconnection syndrome.
Asunto(s)
Enfermedad de Alzheimer , Atrofia , Disfunción Cognitiva , Sustancia Gris , Imagen Multimodal , Tomografía de Emisión de Positrones , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Disfunción Cognitiva/fisiopatología , Atrofia/patología , Anciano , Tomografía de Emisión de Positrones/métodos , Imagen Multimodal/métodos , Masculino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/metabolismo , Femenino , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Amiloide/metabolismo , Imagen de Difusión por Resonancia Magnética/métodosRESUMEN
The human thalamus relays sensory signals to the cortex and facilitates brain-wide communication. The thalamus is also more directly involved in sensorimotor and various cognitive functions but a full characterization of its functional repertoire, particularly in regard to its internal anatomical structure, is still outstanding. As a putative hub in the human connectome, the thalamus might reveal its functional profile only in conjunction with interconnected brain areas. We therefore developed a novel systems-level Bayesian reverse inference decoding that complements the traditional neuroinformatics approach towards a network account of thalamic function. The systems-level decoding considers the functional repertoire (i.e., the terms associated with a brain region) of all regions showing co-activations with a predefined seed region in a brain-wide fashion. Here, we used task-constrained meta-analytic connectivity-based parcellation (MACM-CBP) to identify thalamic subregions as seed regions and applied the systems-level decoding to these subregions in conjunction with functionally connected cortical regions. Our results confirm thalamic structure-function relationships known from animal and clinical studies and revealed further associations with language, memory, and locomotion that have not been detailed in the cognitive neuroscience literature before. The systems-level decoding further uncovered large systems engaged in autobiographical memory and nociception. We propose this novel decoding approach as a useful tool to detect previously unknown structure-function relationships at the brain network level, and to build viable starting points for future studies.