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AbstractDuring infancy, cardiac vagal modulation has been associated with attentional and social engagement behaviors. While studies have shown that infants display a behavioral repertoire that enables them to interact with others by being able to regulate themselves in order to attend to and to discriminate emotional and social cues, vagal modulation to sensory stimuli and its association with behavioral outcomes at early ages remains to be addressed. In this study, we analyzed the cardiac vagal response of 1‐month‐old infants to two auditory stimuli intensities and whether vagal response was associated with social interactive and self‐regulatory abilities. Therefore, we recorded cardiac and respiratory physiological responses in 28 infants using a Biopac System. Neurobehavioral assessment was performed using the Neonatal Behavioral Assessment Scale. We observed increased respiratory sinus arrhythmia (RSA) amplitude to both auditory stimuli intensities when compared to baseline. No intensity effect was found for the RSA response. Additionally, we observed that higher RSA amplitude to both auditory stimuli was positively correlated with adjusted self‐regulatory behaviors, suggesting a convergence between multiple measures assessing infants' state regulation. Results are discussed in light of 1‐month‐old infants' auditory stimuli processing and its implications for regulatory behaviors and the emergent social‐like behaviors.

AbstractResting 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.

Background: GTF2I codes for a general intrinsic transcription factor and calcium channel regulator TFII-I, with high and ubiquitous expression, and a strong candidate for involvement in the morphological and neuro-developmental anomalies of the Williams-Beuren syndrome (WBS). WBS is a genetic disorder due to a recurring deletion of about 1,55-1,83 Mb containing 25-28 genes in chromosome band 7q11.23 including GTF2I. Completed homozygous loss of either the Gtf2i or Gtf2ird1 function in mice provided additional evidence for the involvement of both genes in the craniofacial and cognitive phenotype. Unfortunately nothing is now about the behavioral characterization of heterozygous mice. Methods: By gene targeting we have generated a mutant mice with a deletion of the first 140 amino-acids of TFII-I. mRNA and protein expression analysis were used to document the effect of the study deletion. We performed behavioral characterization of heterozygous mutant mice to document in vivo implications of TFII-I in the cognitive profile of WBS patients. Results: Homozygous and heterozygous mutant mice exhibit craniofacial alterations, most clearly represented in homozygous condition. Behavioral test demonstrate that heterozygous mutant mice exhibit some neurobehavioral alterations and hyperacusis or odynacusis that could be associated with specific features of WBS phenotype. Homozygous mutant mice present highly compromised embryonic viability and fertility. Regarding cellular model, we documented a retarded growth in heterozygous MEFs respect to homozygous or wild-type MEFs. Conclusion: Our data confirm that, although additive effects of haploinsufficiency at several genes may contribute to the full craniofacial or neurocognitive features of WBS, correct expression of GTF2I is one of the main players. In addition, these findings show that the deletion of the fist 140 amino-acids of TFII-I altered it correct function leading to a clear phenotype, at both levels, at the cellular model and at the in vivo model. ; This work was supported by grants from the Spanish Ministry of Health (FIS 04/0433, to VC), the Spanish Ministry of Science and Education (SAF2004-6382, to LPJ and BFU2006-04406/BMC, to JLB) and the VI Framework Programme of the European Union (LSHG-CT-2006-037627, to LPJ). JL was supported by a FPI Fellowship (SAF2001-3941) and VC is a FIS Investigator.