Structure-function relationship of working memory activity with hippocampal and prefrontal cortex volumes

Abstract

A rapidly increasing number of studies are quantifying the system-level network architecture of the human brain based on structural-to-structural and functional-to-functional relationships. However, a largely unexplored area is the nature and existence of "cross-modal" structural-functional relationships, in which, for example, the volume (or other morphological property) of one brain region is related to the functional response to a given task either in that same brain region, or another brain region. The present study investigated whether the gray matter volume of a selected group of structures (superior, middle, and inferior frontal gyri, thalamus, and hippocampus) was correlated with the fMRI response to a working memory task, within a mask of regions previously identified as involved with working memory. The subjects included individuals with schizophrenia, their siblings, and healthy controls (n = 154 total). Using rigorous permutation testing to define the null distribution, we found that the volume of the superior and middle frontal gyri was correlated with working memory activity within clusters in the intraparietal sulcus (i.e., dorsal parietal cortex) and that the volume of the hippocampus was correlated with working memory activity within clusters in the dorsal anterior cingulate cortex and left inferior frontal gyrus. However, we did not find evidence that the identified structure-function relationships differed between subject groups. These results show that long-distance structural-functional relationships exist within the human brain. The study of such cross-modal relationships represents an additional approach for studying systems-level interregional brain networks.

Fig. 1

Regions where the volume of the SFG (blue, clusters numbered 1 and 2), MFG (cyan, cluster number 3), and hippocampus (red, clusters numbered 4 and 5) were correlated with working memory (2-back) task activity at that location across the entire group of subjects (“main effect” model). The ordering of cluster numbers in the figure corresponds to successive rows in Table 1. The analyses were restricted to a working memory mask (based on published meta-analyses), which is shown in yellow. Analyses were conducted in volume space (middle portion of figure showing axial slices spaced by the equivalent of 6.3 mm in MNI152 space). However, for visualization purposes, the intersections of the regions and mask with an average surface (PALS 12 subject average) (Van Essen 2005) in the same stereotaxic space are also shown on the inflated PALS cortical surfaces using Caret (top and bottom). Because of the nature of this volume to surface mapping, portions of cluster number 5 appear disjointed on the medial surface of both the left and right hemispheres, and the extent of cluster number 5 on those surfaces does not accurately reflect the size of that cluster in the volume (greater than 2.5 times larger in volume than clusters 3 and 4, which were the next two largest clusters). Also shown on the surfaces is an outline (white) of the regions (across the whole brain) where there was a statistically significant positive response to the 2-back task versus fixation (assessed using permutation testing with all 154 subjects, without regard to group status). The medial wall of the surfaces includes a representation of the thalamic portion of the analysis mask and activation to the 2-back task. However, the cerebellar portions of the analysis mask are only visible in the volume space and the cerebellar activation to the 2-back task (which was extensive) is not visualized