The structural and functional connectivity of the posterior cingulate cortex: Comparison between deterministic and probabilistic tractography for the investigation of structure–function relationships

Sakh Khalsa,Stephen D Mayhew,Magdalena Chechlacz,Manny Bagary,Andrew P Bagshaw

doi:10.1016/j.neuroimage.2013.12.022

Sakh Khalsa, Stephen D Mayhew + Show 3 more

Open Access

https://doi.org/10.1016/j.neuroimage.2013.12.022

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Abstract

The default mode network (DMN) is one of the most studied resting-state networks, and is thought to be involved in the maintenance of consciousness within the alert human brain. Although many studies have examined the functional connectivity (FC) of the DMN, few have investigated its underlying structural connectivity (SC), or the relationship between the two. We investigated this question in fifteen healthy subjects, concentrating on connections to the precuneus/posterior cingulate cortex (PCC), commonly considered as the central node of the DMN. We used group independent component analysis (GICA) and seed-based correlation analysis of fMRI data to quantify FC, and streamline and probabilistic tractography to identify structural tracts from diffusion tensor imaging (DTI) data. We first assessed the presence of structural connections between the DMN regions identified with GICA. Of the 15 subjects, when using the probabilistic approach 15 (15) demonstrated connections between the PCC and mesial prefrontal cortex (mPFC), 11 (15) showed connections from the PCC to the right inferior parietal cortex (rIPC) and 8 (15) to the left IPC. Next, we assessed the strength of FC (magnitude of temporal correlation) and SC (mean fractional anisotropy of reconstructed tracts (streamline), number of super-threshold voxels within the mask region (probabilistic)). The lIPC had significantly reduced FC to the PCC compared to the mPFC and rIPC. No difference in SC strength between connections was found using the streamline approach. For the probabilistic approach, mPFC had significantly lower SC than both IPCs. The two measures of SC strength were significantly correlated, but not for all paired connections. Finally, we observed a significant correlation between SC and FC for both tractography approaches when data were pooled across PCC–lIPL, PCC–rIPL and PCC–mPFC connections, and for some individual paired connections. Our results suggest that the streamline approach is advantageous for characterising the connectivity of long white matter tracts (PCC–mPFC), whilst the probabilistic approach was more reliable at identifying PCC–IPC connections. The direct comparison of FC and SC indicated that pairs of nodes with stronger structural connections also had stronger functional connectivity, and that this was maintained with both tractography approaches. Whilst the definition of SC strength remains controversial, our results could be considered to provide some degree of validation for the measures of SC strength that we have used. Direct comparisons of SC and FC are necessary in order to understand the structural basis of functional connectivity, and to characterise and quantify the changes in the brain's functional architecture that occur as a result of normal physiology or pathology.

Highlights

In the current study we focused on the default mode network (DMN) as one of the most reliably detected resting-state networks (RSNs), whose spatiotemporal pattern of activity has been observed to be altered in a range of neurological and psychiatric disorders (Broyd et al, 2009), as well as during altered states of consciousness such as sleep (Horovitz et al, 2009; Sämann et al, 2010), coma (Norton et al, 2012) and anaesthesia (Fiset et al, 1999)
Regions of Interest (ROI): precuneus cortex (PCC), medial prefrontal/anterior cingulate cortex (mPFC) and left and right IPC. We focused on these four ROIs as they have been consistently reported as constituting robust regions of the DMN (Damoiseaux and Greicius, 2009; Greicius et al, 2003; Horovitz et al, 2009; Raichle et al, 2001)
Seed-based functional connectivity (FC) was used to measure the strength of FC for each pairwise connection between the PCC seed and the mPFC, left inferior parietal cortex/angular gyrus (lIPC), and right inferior parietal cortex/angular gyrus (rIPC)

Summary

Introduction

The human brain is organised into a series of functional networks that exhibit correlations in activity between individual regions even in the absence of stimulation (Biswal et al, 1995; Gusnard et al, 2001; Raichle et al, 2001; Shulman et al, 1997). Whilst a number of different tractography algorithms of varying complexity exist, the two main distinguishing factors relate to how white matter tracts are modelled within a voxel (i.e. a single or multiple fibre orientations) and how the tracts are reconstructed (i.e. interpolated streamlines or probabilistic global connectivity estimations). These choices can have a profound effect on the estimated white matter fibre tracts, and on the judgement of whether two brain regions are structurally connected (Yo et al, 2009). The added value of investigating the relationship between SC and FC has recently been highlighted in patients with idiopathic generalised epilepsy (Zhang et al, 2011) and traumatic brain injury (Kinnunen et al, 2011)

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