Dynamic Causal Modeling of Hippocampal Links within the Human Default Mode Network: Lateralization and Computational Stability of Effective Connections

Vadim Ushakov, Maksim G. Sharaev, Sergey I. Kartashov, Viktoria V. Zavyalova, Vitaliy M. Verkhlyutov, Boris M. Velichkovsky

The purpose of this paper was to study causal relationships between left and right hippocampal regions (LHIP and RHIP, respectively) within the default mode network (DMN) as represented by its key structures: the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and the inferior parietal cortex of left (LIPC) and right (RIPC) hemispheres. Furthermore, we were interested in testing the stability of the connectivity patterns when adding or deleting regions of interest. The functional magnetic resonance imaging (fMRI) data from a group of 30 healthy right-handed subjects in the resting state were collected and a connectivity analysis was performed. To model the effective connectivity, we used the spectral Dynamic Causal Modeling (DCM). Three DCM analyses were completed. Two of them modeled interaction between five nodes that included four DMN key structures in addition to either LHIP or RHIP. The last DCM analysis modeled interactions between four nodes whereby one of the main DMN structures, PCC, was excluded from the analysis. The results of all DCM analyses indicated a high level of stability in the computational method: those parts of the winning models that included the key DMN structures demonstrated causal relations known from recent research. However, we discovered new results as well. First of all, we found a pronounced asymmetry in LHIP and RHIP connections. LHIP demonstrated a high involvement of DMN activity with preponderant information outflow to all other DMN regions. Causal interactions of LHIP were bidirectional only in the case of LIPC. On the contrary, RHIP was primarily affected by inputs from LIPC, RIPC, and LHIP without influencing these or other DMN key structures. For the first time, an inhibitory link was found from MPFC to LIPC, which may indicate the subjects' effort to maintain a resting state. Functional connectivity data echoed these results, though they also showed links not reflected in the patterns of effective connectivity. We suggest that such lateralized architecture of hippocampal connections may be related to lateralization phenomena in verbal and spatial domains documented in human neurophysiology, neuropsychology, and neurolinguistics.