Multimodal Neuroimaging of Gene-Brain Relationships in Williams Syndrome

综合神经影像学部分通过对威廉姆斯综合征（WS）个体和精心匹配的对照志愿者进行多模式神经影像学研究，在阐明大脑结构和功能的特定遗传贡献方面取得了实质性进展（研究10-M-0112， NCT01132885; 00-M-0085, NCT00004571）。近年来，我们通过多模态神经成像实验证明，在这种情况下，特征性的视觉空间构建缺陷的神经基质没有受到早期视觉皮质功能的影响，但破坏了顶叶内沟区神经完整性、空间判断过程中的激活和结构。

The Section on Integrative Neuroimaging has made substantial progress toward elucidating specific genetic contributions to brain structure and function through multimodal neuroimaging studies of Williams Syndrome (WS) individuals and carefully matched comparison volunteers (Study 10-M-0112, NCT01132885; 00-M-0085, NCT00004571). We have in recent years identified the neural substrates of the characteristic visuospatial construction deficits in this condition by demonstrating via multi-modal neuroimaging experiments spared early visual cortical functioning, but disrupted intraparietal sulcal region neural integrity, activation during spatial judgments, and structure. In addition to visuospatial impairments, WS individuals harbor dyadic contrapuntal socio-emotional functioning, such that hypersociability is coupled with heightened non-social anxiety. This dramatic aspect of WS, with obvious implications for understanding neurogenetic bases for social cognition and anxiety generally, serves as a second focus of our research, and we have had considerable success in identifying plausible systems-level correlates of these phenotypes. In particular, we have found decreased fearful face stimuli evoked amygdala activation in WS for compared to IQ matched healthy controls and conversely, an increased in amygdala response in WS to non-social frightening stimuli as compared with matched healthy control participants. Importantly, using structural equation modeling, we found these differences to be linked to altered prefrontal regulation. We have also identified convergent alterations in anterior insula structure, function, and inter-regional connectivity, which predict the characteristic Williams syndrome (WS) personality. (Jabbi et al., 2012) An integral part of the WS phenotype is vascular abnormalities, most commonly supravalvular aortic stenosis and peripheral pulmonary artery stenosis, which have been attributed to hemideletion of the WS-region gene, elastin. Because elastin may be important in defining the structure of intracerebral vasculature, we sought to identify whether WS individuals with deletions that included elastin were at increased risk for clinically meaningful anomalous cerebrovasculature. Using magnetic resonance angiography, we found no evidence for abnormal dilation or stenosis of intracranial vessels (Wint et al., 2013). Perhaps the greatest recent advancement made by the Section, however, has been the successful launch and active data acquisition for longitudinal multimodal neuroimaging studies of WS children. Though data accrual will require years of careful and concerted effort, the potential for these studies to shed unprecedented light on genetic contributions to brain development are enormous. In sum, our efforts have resulted in the identification of candidate neurofunctional substrates for hallmark neuropsychological abnormalities in WS, reassuring evidence for sparing of intracerebral vasculature, and continued progress toward better defining the precise genetic, developmental and neurochemical contributions toward the WS neurophenotype is ongoing. In sum, our efforts have resulted in the identification of candidate neurofunctional substrates for hallmark neuropsychological abnormalities in WS, reassuring evidence for sparing of intracerebral vasculature, and continued progress toward better defining the precise genetic, developmental and neurochemical contributions toward the WS neurophenotype is ongoing.