Toward neuroimaging-based network biomarkers for transient ischemic attack

Stroke is associated with topological disruptions of large-scale functional brain networks. However, whether these disruptions occur in transient ischemic attack (TIA), an important risk factor for stroke, remains largely unknown. Combining multimodal MRI techniques, we systematically examined TIA-related topological alterations of functional brain networks, and tested their reproducibility, structural, and metabolic substrates, associations with clinical risk factors and abilities as diagnostic and prognostic biomarkers. We found that functional networks in patients with TIA exhibited decreased whole-brain network efficiency, reduced nodal centralities in the bilateral insula and basal ganglia, and impaired connectivity of inter-hemispheric communication. These alterations remained largely unchanged when using different brain parcellation schemes or correcting for micro head motion or for regional gray matter volume, cerebral blood flow or hemodynamic lag of BOLD signals in the patients. Moreover, some alterations correlated with the levels of high-density lipoprotein cholesterol (an index related to ischemic attacks via modulation of atherosclerosis) in the patients, distinguished the patients from healthy individuals, and predicted future ischemic attacks in the patients. Collectively, these findings highlight the emergence of characteristic network dysfunctions in TIA, which may aid in elucidating pathological mechanisms and establishing diagnostic and prognostic biomarkers for the disease.