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

Abstract

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.

The effect of global signal regression on DCM estimates of noise and effective connectivity from resting state fMRI

“…Remarkably, the within-network connectivity was very similar when networks were estimated separately compared to networks as a whole (compare e.g., Figure 5 and 6). This was also found by Ushakov et al (2016), who showed that connectivity within the core DMN was very similar when either left or right hippocampus was included in the network. This shows that group-level resting-state DCM results are quite robust against addition of extra networks and regions.…”

Variability and reliability of effective connectivity within the core default mode network: A longitudinal spectral DCM study

“…Both studies found reciprocal positive connectivity between IPC, and positive projections from lateral to medial brain regions. Ushakov et al (2016) showed that adding extra regions (i.e., left and right parahippocampal gyri) to the four-region DMN did not have a substantial impact on its effective connectivity pattern. Zhou et al (2018) showed that the salience and dorsal attention network have a negative influence on the core DMN, while the converse influence was slightly positive.…”

“…Most research using empirical data has focused on effective connectivity within the default mode network (e.g., Razi et al, 2015;Sharaev et al, 2016;Ushakov et al, 2016;Zhou et al 2018). Both Razi et al (2015) and Sharaev et al, 2016 estimated connectivity within the 'core' DMN, which included left and right intraparietal cortices (IPC), medial prefrontal cortex (mPFC), and posterior cingulate cortex (PCC).…”

Cognitive science: The art and its implications

“…This convergence of methodologies seems to lead to a convergence in results. To be more specific, I will address several implications of the recent discovery which demonstrated a profound asymmetry in effective (cause-and-effect) connections between the left and right hippocampi within the human default mode network, or DMN (Ushakov et al, 2016). The latter is a set of functionally and structurally connected brain areas that are activated at rest and deactivated by external stimulation.…”

“…Recent neuroimaging studies of the DMN bring together both concepts by showing that activity around the right temporoparietal junction is the best predictor of working memory scores (Markett et al, 2017). This region in turn is the main input pathway to the right hippocampus within the DMN connectome (see Ushakov et al, 2016Ushakov et al, , velichkovsky et al, 2017.…”