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

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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.

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Notes

  1. Maps of positive activation computed separately for the word versus fixation and face versus fixation versions of the 2-back task (assessed using permutation testing with all 154 subjects, without regard to group status) were substantially overlapping, with a union overlap (Jaccard coefficient) of 0.72 and a mean overlap (Dice coefficient) of 0.84. This high degree of overlap of regions activated by word- and face-specific working memory stimuli is consistent with meta-analyses of working memory, which find broadly similar activation patterns for different content material (e.g., verbal vs. nonverbal), albeit with support for some limited content-specific dissociations in activation (Wager and Smith 2003; Owen et al. 2005).

  2. Notwithstanding these justifications for including all subjects in the main effects analysis, we conducted a supplementary analysis involving only the 93 healthy participants. In this analysis, the structure–function correlation between hippocampal volume and WM activity remained significant for the clusters in the left IFG and dorsal ACC (yielding clusters analogous to 4 and 5 in Fig. 1; P < 0.003 for the extent of both clusters based on permutation testing). However, no clusters analogous to clusters 1–3 of Fig. 1 survived when using just the 93 healthy participants.

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Acknowledgments

We thank the staff of the Administration/Assessment Core of the CCNMD at Washington University School of Medicine for collection of the clinical and imaging data. This work was supported by the National Institute of Mental Health [MH071616, MH056584] and the National Center for Research Resources [RR015241].

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  1. Department of Psychiatry, Washington University School of Medicine, Box 8134, 660 S. Euclid Ave., St. Louis, MO, 63110, USA

    Michael P. Harms & Deanna M. Barch

  2. Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Lei Wang & John G. Csernansky

  3. Department of Psychology, Washington University, St. Louis, MO, USA

    Deanna M. Barch

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Correspondence to Michael P. Harms.

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Harms, M.P., Wang, L., Csernansky, J.G. et al. Structure–function relationship of working memory activity with hippocampal and prefrontal cortex volumes. Brain Struct Funct 218, 173–186 (2013). https://doi.org/10.1007/s00429-012-0391-8

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