Mapping the effect of the X chromosome on the human brain: Neuroimaging evidence from Turner syndrome

•The X chromosome has been shown to play a crucial role in human brain and behavior.•Turner syndrome (TS) is a human knockout model for studying X chromosome functions.•TS neuroimaging studies using multi-modal MRI techniques are thoroughly reviewed.•Various neuroimaging-based phenotypes have been demonstrated to be abnormal in TS.•The brain may mediate or moderate the X chromosome-behavior relations.

In addition to determining sex, the X chromosome has long been considered to play a crucial role in brain development and intelligence. Turner syndrome (TS) is caused by the congenital absence of all or part of one of the X chromosomes in females. Thus, Turner syndrome provides a unique “knock-out model” for investigating how the X chromosome influences the human brain in vivo. Numerous cutting-edge neuroimaging techniques and analyses have been applied to investigate various brain phenotypes in women with TS, which have yielded valuable evidence toward elucidating the causal relationship between the X chromosome and human brain structure and function. In this review, we comprehensively summarize the recent progress made in TS-related neuroimaging studies and emphasize how these findings have enhanced our understanding of X chromosome function with respect to the human brain. Future investigations are encouraged to address the issues of previous TS neuroimaging studies and to further identify the biological mechanisms that underlie the function of specific X-linked genes in the human brain.