The Effects of the X Chromosome on Intrinsic Functional Connectivity in the Human Brain: Evidence from Turner Syndrome Patients

Cereb Cortex. 2017 Jan 1;27(1):474-484. doi: 10.1093/cercor/bhv240.

Abstract

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.

Keywords: Turner syndrome; functional module; intrinsic functional connectivity; resting state functional MRI; the X chromosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Brain / physiopathology*
  • Brain Mapping
  • Child
  • Chromosomes, Human, X*
  • Cognition Disorders / etiology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Neural Pathways / physiopathology*
  • Turner Syndrome / genetics
  • Turner Syndrome / physiopathology*