title: High-Resolution Functional Connectivity Density: Hub Locations, Sensitivity, Specificity, Reproducibility, and Reliability.
abstract: Brain regions with high connectivity have high metabolic cost and their disruption is associated with neuropsychiatric disorders. Prior neuroimaging studies have identified at the group-level local functional connectivity density ( L: FCD) hubs, network nodes with high degree of connectivity with neighboring regions, in occipito-parietal cortices. However, the individual patterns and the precision for the location of the hubs were limited by the restricted spatiotemporal resolution of the magnetic resonance imaging (MRI) measures collected at rest. In this work, we show that MRI datasets with higher spatiotemporal resolution (2-mm isotropic; 0.72 s), collected under the Human Connectome Project (HCP), provide a significantly higher precision for hub localization and for the first time reveal L: FCD patterns with gray matter (GM) specificity >96% and sensitivity >75%. High temporal resolution allowed effective 0.01-0.08 Hz band-pass filtering, significantly reducing spurious L: FCD effects in white matter. These high spatiotemporal resolution L: FCD measures had high reliability [intraclass correlation, ICC(3,1) > 0.6] but lower reproducibility (>67%) than the low spatiotemporal resolution equivalents. GM sensitivity and specificity benchmarks showed the robustness of L: FCD to changes in model parameter and preprocessing steps. Mapping individual's brain hubs with high sensitivity, specificity, and reproducibility supports the use of L: FCD as a biomarker for clinical applications in neuropsychiatric disorders.
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Dardo
authors.initials: D
authors.lastname: Tomasi
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Shokri-Kojori
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA National Institute on Drug Abuse, Bethesda, MD, USA.
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000502:physiology*; D063132:Connectome / Q000379:methods; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000502:physiology; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000502:physiology; D015203:Reproducibility of Results; D012146:Rest; D012680:Sensitivity and Specificity
keywords: FCDM; aging; global signal regression; motion; multiband; physiologic noise; resting state