Topographic functional interactions between caudate and cortex are organized by network and degrade with age

Abstract

The striatum is postulated to play a role in gating cortical processing during goal-oriented behavior. However, the underlying circuit structure for striatal gating remains unclear. Deviating from previous approaches which typically treat the striatum as a homogenous structure or small compartments, we took a functional connectivity approach that utilizes the entire anatomical space of the caudate nucleus and examined its functional relationship with the cortex and how that relationship changes with age. We defined the topography of the caudate functional connectivity with the rest of the brain using three publicly available resting-state fMRI data samples. There were several key findings. First, our results revealed two stable gradients of connectivity patterns across the caudate: medial-lateral (M-L) and anterior-posterior (A-P) axes, which supports findings in previous anatomical studies of non-human primates that there is more than one organizational principle. Second, the differential connectivity patterns along the caudates M-L gradient were not limited to single structures but rather organized with respect to large-scale neural networks; in particular, networks associated with internal orienting behavior are closely linked to the medial extent of the caudate whereas networks associated with external orienting behavior are closely linked to the lateral extent of the caudate. Third, we found a decrease in the integrity of M-L organization with healthy aging which was associated with age-related changes in behavioral measures of flexible control. In sum, the caudate shows a topographic organization with respect to large-scale networks in the human brain and changes this organization seem to have implications for age-related decline in flexible control of behavior.