Altered functional connectivity of the default mode network in Williams syndrome: a multimodal approach

Abstract

Resting state brain networks are implicated in a variety of relevant brain functions. Importantly, abnormal patterns of functional connectivity (FC) have been reported in several neurodevelopmental disorders. In particular, the Default Mode Network (DMN) has been found to be associated with social cognition. We hypothesize that the DMN may be altered in Williams syndrome (WS), a neurodevelopmental genetic disorder characterized by an unique cognitive and behavioral phenotype. In this study, we assessed the architecture of the DMN using fMRI in WS patients and typically developing matched controls (sex and age) in terms of FC and volumetry of the DMN. Moreover, we complemented the analysis with a functional connectome approach. After excluding participants due to movement artifacts (n = 3), seven participants with WS and their respective matched controls were included in the analyses. A decreased FC between the DMN regions was observed in the WS group when compared with the typically developing group. Specifically, we found a decreased FC in a posterior hub of the DMN including the precuneus, calcarine and the posterior cingulate of the left hemisphere. The functional connectome approach showed a focalized and global increased FC connectome in the WS group. The reduced FC of the posterior hub of the DMN in the WS group is consistent with immaturity of the brain FC patterns and may be associated with the singularity of their visual spatial phenotype.

Increased overall cortical connectivity with syndrome specific local decreases suggested by atypical sleep-EEG synchronization in Williams syndrome

“…Reported global interhemispheric and between network overconnectivity of subjects with Williams syndrome is a similar fMRI finding 20, 21 . In addition, the increased number of synapses and dendritic spines in a Williams syndrome model based on human induced pluripotent stem cells 22 could be the anatomical-microstructural basis of our finding.…”

“…In addition to the strong support for a broadband overconnectivity of neural networks in Williams syndrome subjects, specific DMN hubs and networks are underconnected in this developmental disability 20, 21 . Indeed, we have found sleep state-, frequency-, and region-specific decreases in EEG synchronization in our current study.…”

“…An important methodological aspect is that EEG recordings, which are much more feasible in subjects with developmental disabilities are suitable for unravelling the peculiarities of network synchronization in Williams syndrome, hitherto established exclusively with fMRI recordings. Another relevant aspect to be emphasized is that the (between network) overconnectivity reported in the two recent fMRI investigations of resting Williams syndrome subjects 20, 21 can be generalized to NREM and REM sleep as well. This latter aspect of a state-independent neural overconnectivity in Williams syndrome subjects indicates a potential structural basis of the observed sleep alterations, which could be further characterized by neuroimaging methods unravelling the properties of white matter tracts.…”

“…The specific sleep-EEG alterations of Williams syndrome subjects revealed by our team so far 8, 10, 12, 19 lead us to focus on the synchronization properties of NREM and REM sleep EEG of subjects with Williams syndrome. Recent resting state fMRI investigations of Williams syndrome populations revealed a peculiar pattern of Default Mode Network (DMN) underconnectivity together with a concomitant global interhemispheric and between network overconnectivity 20, 21 . Furthermore, altered network connectivity, longer total dendrites, as well as an increased number of spines and synapses are characteristic features of a Williams syndrome model based on human induced pluripotent stem cells 22 .…”

Autism and Williams syndrome: dissimilar socio-cognitive profiles with similar patterns of abnormal gene expression in the blood

“…Regarding the associations between irregularities in certain brain networks and some core social deficits found in both ASD and WS, four networks are worth considering. The first is the default mode network, associated with various elements of social cognition, which includes the medial prefrontal cortex (mPFC), the posterior cingulate cortex (PCC), the precuneus, the inferior parietal lobes (IPL), and medial temporal regions; its functional connectivity has been found to be irregular in ASD (Assaf et al, 2010;Lynch et al, 2013) as well as WS (Sampaio et al, 2016). Even more relevant is the second network, namely, the social brain network, which includes the superior temporal sulcus (STS), the anterior cingulate cortex (ACC), the medial prefrontal cortex (mPFC), the inferior frontal gyrus (IFG), and the anterior insula and the amygdala.…”