Functional Network Mirrored in the Prefrontal Cortex, Caudate Nucleus, and Thalamus: High-Resolution Functional Imaging and Structural Connectivity

Despite myriads of studies on a parallel organization of cortico-striatal-thalamo-cortical loops, direct evidence of this has been lacking for the healthy human brain. Here, we scrutinize the functional specificity of the cortico-subcortical loops depending on varying levels of cognitive hierarchy as well as their structural connectivity with high-resolution fMRI and diffusion-weighted MRI (dMRI) at 7 tesla. Three levels of cognitive hierarchy were implemented in two domains: second language and nonlanguage. In fMRI, for the higher level, activations were found in the ventroanterior portion of the prefrontal cortex (PFC), the head of the caudate nucleus (CN), and the ventral anterior nucleus (VA) in the thalamus. Conversely, for the lower level, activations were located in the posterior region of the PFC, the body of the CN, and the medial dorsal nucleus (MD) in the thalamus. This gradient pattern of activations was furthermore shown to be tenable by the parallel connectivity in dMRI tractography connecting the anterior regions of the PFC with the head of the CN and the VA in the thalamus, whereas the posterior activations of the PFC were linked to the body of the CN and the MD in the thalamus. This is the first human in vivo study combining fMRI and dMRI showing that the functional specificity is mirrored within the cortico-subcortical loop substantiated by parallel networks.