The goal of the NeuroBase project is to facilitate collaborative research in neuroimaging through a federated system based on semantic web technologies. The cornerstone and focus of this paper is the design of a common semantic model providing a unified view on all data and tools to be shared. For this purpose, we built a multi-layered and multi-components formal ontology. This paper presents two major contributions. The first is related to the general methodology we propose for building an application ontology based on consistent conceptualization choices provided by the DOLCE foundational ontology and core ontologies of domains that we reuse; the second concerns the domain ontology we designed for neuroimaging, which encompasses both the objective nature of image data and the subjective nature of image content, through annotations based on regions of interest made by agents (humans or computer programs). We report on realistic domain use-case queries referring to our application ontology.