The Effects of the X Chromosome on Intrinsic Functional Connectivity in the Human Brain: Evidence from Turner Syndrome Patients.
Turner syndrome (TS), a disorder caused by the congenital absence of one of the 2 X chromosomes in female humans, provides a valuable human "knockout model" for studying the functions of the X chromosome. At present, it remains unknown whether and how the loss of the X chromosome influences intrinsic functional connectivity (FC), a fundamental phenotype of the human brain. To address this, we performed resting-state functional magnetic resonance imaging and specific cognitive assessments on 22 TS patients and 17 age-matched control girls. A novel data-driven approach was applied to identify the disrupted patterns of intrinsic FC in TS. The TS girls exhibited significantly reduced whole-brain FC strength within the bilateral postcentral gyrus/intraparietal sulcus, angular gyrus, and cuneus and the right cerebellum. Furthermore, a specific functional subnetwork was identified in which the intrinsic FC between nodes was mostly reduced in TS patients. Particularly, this subnetwork is composed of 3 functional modules, and the disruption of intrinsic FC within one of these modules was associated with the deficits of TS patients in math-related cognition. Taken together, these findings provide novel insight into how the X chromosome affects the human brain and cognition, and emphasize an important role of X-linked genes in intrinsic neural coupling.
Department of Radiology.
Sheng
S
Xie
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
Jiaotian
J
Yang
Department of Pediatrics, China-Japan Friendship Hospital, Beijing 100029, China.
Zhixin
Z
Zhang
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
Chenxi
C
Zhao
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
Yanchao
Y
Bi
Department of Pediatrics, China-Japan Friendship Hospital, Beijing 100029, China.
Qiuling
Q
Zhao
Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Hui
H
Pan
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
Gaolang
G
Gong
D000293:Adolescent; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D041321:Chromosomes, Human, X; D003072:Cognition Disorders / Q000209:etiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009434:Neural Pathways / Q000503:physiopathology*; D014424:Turner Syndrome / Q000235:genetics / Q000503:physiopathology*
Turner syndrome; functional module; intrinsic functional connectivity; resting state functional MRI; the X chromosome