In addition to the assessment of local alterations of specific brain regions, the investigation of entire networks with in vivo neuroimaging techniques has gained increasing attention. In general, connectivity analysis refers to the investigation of links between brain regions, with the aim to characterize their interactions and information transfer. These may represent or relate to different physiological characteristics (structural, functional, or metabolic information) and can be calculated across different levels of granularity (2 regions vs whole brain). In this article, we provide an overview of different connectivity analysis approaches with interpretations and limitations as well as examples in pharmacological imaging and clinical applications. Structural connectivity obtained from diffusion MRI enables the reconstruction of neuronal fiber tracts. These physical links represent major constraints of functional connections, which are in turn defined as correlations between signal time courses. In addition, molecular connectivity approaches based on PET imaging enable the assessment of interregional associations of metabolic demands and neurotransmitter systems. Application of these approaches in clinical investigations has demonstrated novel alterations in various neurological and psychiatric disorders on a network level. Future work should aim for the combined assessment of multiple imaging modalities and to establish robust biomarkers for clinical use. These advancements will further improve the biological interpretation of connectivity metrics and networks of the human brain.
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