title: Characterizing individual differences in functional connectivity using dual-regression and seed-based approaches.
abstract: A central challenge for neuroscience lies in relating inter-individual variability to the functional properties of specific brain regions. Yet, considerable variability exists in the connectivity patterns between different brain areas, potentially producing reliable group differences. Using sex differences as a motivating example, we examined two separate resting-state datasets comprising a total of 188 human participants. Both datasets were decomposed into resting-state networks (RSNs) using a probabilistic spatial independent component analysis (ICA). We estimated voxel-wise functional connectivity with these networks using a dual-regression analysis, which characterizes the participant-level spatiotemporal dynamics of each network while controlling for (via multiple regression) the influence of other networks and sources of variability. We found that males and females exhibit distinct patterns of connectivity with multiple RSNs, including both visual and auditory networks and the right frontal-parietal network. These results replicated across both datasets and were not explained by differences in head motion, data quality, brain volume, cortisol levels, or testosterone levels. Importantly, we also demonstrate that dual-regression functional connectivity is better at detecting inter-individual variability than traditional seed-based functional connectivity approaches. Our findings characterize robust-yet frequently ignored-neural differences between males and females, pointing to the necessity of controlling for sex in neuroscience studies of individual differences. Moreover, our results highlight the importance of employing network-based models to study variability in functional connectivity.
authors.affiliation: Center for Cognitive Neuroscience, Duke University, Durham, NC 27708, USA; Department of Psychology and Neuroscience, Duke University, Durham, NC 27708, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Smith
authors.affiliation: Center for Cognitive Neuroscience, Duke University, Durham, NC 27708, USA.
authors.forename: Amanda V
authors.initials: AV
authors.lastname: Utevsky
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Bland
authors.affiliation: Center for Cognitive Neuroscience, Duke University, Durham, NC 27708, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Clement
authors.affiliation: Division of the Humanities and Social Sciences, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Clithero
authors.affiliation: Center for Cognitive Neuroscience, Duke University, Durham, NC 27708, USA.
authors.forename: Anne E W
authors.initials: AE
authors.lastname: Harsch
authors.affiliation: Center for Cognitive Neuroscience, Duke University, Durham, NC 27708, USA.
authors.forename: R
authors.initials: R
authors.lastname: McKell Carter
authors.affiliation: Center for Cognitive Neuroscience, Duke University, Durham, NC 27708, USA; Department of Psychology and Neuroscience, Duke University, Durham, NC 27708, USA. Electronic address: scott.huettel@duke.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Huettel
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007206:Individuality; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D012044:Regression Analysis; D012727:Sex Characteristics; D055815:Young Adult
keywords: Dual-regression analysis; Functional connectivity; Independent component analysis; Individual differences; Seed-based analysis; Split-sample validation