Estimates of projection overlap and zones of convergence within frontal-striatal circuits

Abstract

Frontal-striatal circuits underlie important decision processes, and pathology in these circuits is implicated in many psychiatric disorders. Studies have shown a topographic organization of cortical projections into the striatum. However, work has also shown that there is considerable overlap in the striatal projection zones of nearby cortical regions. To characterize this in detail, we quantified the complete striatal projection zones from 34 cortical injection locations in rhesus monkeys. We first fit a statistical model that showed that the projection zone of a cortical injection site could be predicted with considerable accuracy using a cross-validated model estimated on only the other injection sites. We then examined the fraction of overlap in striatal projection zones as a function of distance between cortical injection sites, and found that there was a highly regular relationship. Specifically, nearby cortical locations had as much as 80% overlap, and the amount of overlap decayed exponentially as a function of distance between the cortical injection sites. Finally, we found that some portions of the striatum received inputs from all the prefrontal regions, making these striatal zones candidates as information-processing hubs. Thus, the striatum is a site of convergence that allows integration of information spread across diverse prefrontal cortical areas.

Figure 1.

Cortical injection sites.

Figure 2.

Predicted (heat map) and actual (black dots) projections into the striatum from four different cortical injections.

Figure 3.

Deviation between predicted and measured centroid of striatal projection zone.

Figure 4.

Measured fraction of overlap in striatal projection volume as a function of distance between cortical injection sites. Black line given by the following: overlap equals 0.04e^3.2d−0.2. Blue line given by average in each of 20 bins with an equal number of points in each. Right, Proportion of the sample (red dots) that have the indicated overlap. This is calculated by summing the number of red dots in each overlap bin (bar on the bar graph) and dividing by the total number of dots.

Figure 5.

Examples of overlap. Each plot shows a heat map (color bar as in Fig. 2, where saturated red is a probability of 1). The black dots are the voxels that actually received a projection. A, Striatal projection zones of an injection in area 25/14 (top row), area 32 (middle row), and area 9/46 (bottom row). B, Striatal projection zones of injections in areas 11 (top row), 9 (middle row), and 24 (bottom row).

Figure 6.

Properties of striatal projections examined separately for frontal regions. A, Total projection volume of each injection by frontal region. B, Residual fraction of overlap, after accounting for distance between injections.

Figure 7.

Areas of convergence in the striatum. Color on each section indicates voxels that receive projections from 0 to 5 prefrontal cortical regions (i.e., vmPFC, OFC, dACC, dPFC, vlPFC). Numbers indicate distance in millimeters anterior to anterior commissure.