Ellison-Wright Zoë, Heyman Isobel, Frampton Ian, Rubia Katya, Chitnis Xavier, Ellison-Wright Ian, Williams Steve C R, Suckling John, Simmons Andrew, Bullmore Edward
Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
Eur J Neurosci. 2004 Mar;19(6):1505-12. doi: 10.1111/j.1460-9568.2004.03236.x.
Recent progress in developmental neurobiology and neuroimaging can be drawn together to provide new insight into the links between genetically specified processes of embryonic brain development and adult human brain structure and function. We used magnetic resonance imaging (MRI) to show that individuals with aniridia and deficits in executive and social cognition, due to heterozygous mutation of the neurodevelopmental control gene PAX6, have structural abnormalities of grey matter in anterior cingulate cortex, cerebellum and medial temporal lobe, as well as white matter deficits in corpus callosum. Functional MRI demonstrated reduced activation of fronto-striato-thalamic systems during performance of overt verbal fluency and nonsense sentence completion; the most consistent abnormality of verbal executive activation was located in the thalamus. These results provide the first evidence for brain functional differences in humans with PAX6 mutation that are compatible both with anatomical abnormalities in the same subjects and, more circumstantially, with the known roles of murine Pax6 in regional differentiation, axonal guidance and other aspects of early forebrain development. Highly conserved homeobox genes may be critical for normal ontogenesis of large-scale neurocognitive networks supporting phylogenetically advanced mental functions.
发育神经生物学和神经影像学的最新进展可以结合起来，为胚胎脑发育的基因特定过程与成人大脑结构和功能之间的联系提供新的见解。我们使用磁共振成像（MRI）显示，由于神经发育控制基因PAX6的杂合突变而患有无虹膜以及执行和社会认知缺陷的个体，其前扣带回皮质、小脑和内侧颞叶存在灰质结构异常，胼胝体也存在白质缺陷。功能MRI显示，在进行明显的语言流畅性和无意义句子完成任务时，额-纹状体-丘脑系统的激活减少；语言执行激活最一致的异常位于丘脑。这些结果首次证明了PAX6突变人类的脑功能差异，这些差异既与同一受试者的解剖学异常相符，也更间接地与小鼠Pax6在区域分化、轴突导向和早期前脑发育的其他方面的已知作用相符。高度保守的同源框基因可能对支持系统发育上高级心理功能的大规模神经认知网络的正常个体发生至关重要。
