Functional connectivity predicts changes in attention observed across minutes, days, and months Monica D. Rosenberga,b,1, Dustin Scheinostc,d,e,f, Abigail S. Greenef, Emily W. Averyb, Young Hye Kwonb, Emily S. Finng, Ramachandran Ramanih, Maolin Qiuc, R. Todd Constablec,f,i, and Marvin M. Chunb,f,j aDepartment of Psychology, University of Chicago, Chicago, IL 60637; bDepartment of Psychology, Yale University, New Haven, CT 06520; cDepartment of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06510; dChild Study Center, Yale School of Medicine, New Haven, CT 06510; eDepartment of Statistics and Data Science, Yale University, New Haven, CT 06520; fInterdepartmental Neuroscience Program, Yale University, New Haven, CT 06520; gSection on Functional Imaging Methods, Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD 20892; hDepartment of Anesthesiology, University of Florida College of Medicine, Gainesville, FL 32610; iDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT 06510; and jDepartment of Neuroscience, Yale School of Medicine, New Haven, CT 06510 Edited by Michael I. Posner, University of Oregon, Eugene, OR, and approved January 6, 2020 (received for review July 17, 2019) The ability to sustain attention differs across people and changes single measure of functional brain architecture using an entire within a single person over time. Although recent work has dem- neuroimaging-signal time series. The most extensively validated onstrated that patterns of functional brain connectivity predict connectome-based predictive model (CPM), the sustained attention individual differences in sustained attention, whether these same CPM (33), has generalized across six independent datasets to patterns capture fluctuations in attention within individuals remains predict individuals’ overall sustained attention function from func- unclear. Here, across five independent studies, we demonstrate that tional connectivity measured during rest and five different tasks the sustained attention connectome-based predictive model (33–37). Derived using a data-driven technique (38), the sustained (CPM), a validated model of sustained attention function, gen- attention CPM comprises a distributed “high-attention” network of eralizes to predict attentional state from data collected across functional connections, or edges, stronger in individuals with better minutes, days, weeks, and months. Furthermore, the sustained sustained attention function and a “low-attention” network of edges attention CPM is sensitive to within-subject state changes induced stronger in individuals with worse sustained attention.Inotherwords, by propofol as well as sevoflurane, such that individuals show previous work shows that the sustained attention CPM, a model based functional connectivity signatures of stronger attentional states on static functional brain connectivity, predicts individual differences NEUROSCIENCE when awake than when under deep sedation and light anesthesia. in sustained attention function. These predictions can be generated Together, these results demonstrate that fluctuations in attentional from either task-based or resting-state functional connectivity. state reflect variability in the same functional connectivity patterns Do the sustained attention CPM’s high- and low-attention that predict individual differences in sustained attention. networks, which predict a person’s overall ability to maintain focus, also reflect fluctuations in attentional state? Evidence sustained attention | attention fluctuations | individual differences | does suggest that the sustained attention CPM is sensitive to at- functional connectivity | predictive modeling tention improvements following a pharmacological manipulation. That is, healthy adults given a single dose of methylphenidate, a PSYCHOLOGICAL AND COGNITIVE SCIENCES s anyone who has struggled to sit through an esoteric film or common attention-deficit hyperactivity disorder treatment, show Areached the end of a paragraph without comprehending its higher high-attention network strength and lower low-attention content recognizes, we do not sustain a continuous level of at- network strength than unmedicated controls (34). However, this tention at every point in time. Rather, we are frequently distracted between-subjects study did not directly test whether changes in by our external environment and our own internal thoughts, and our level of focus fluctuates—intentionally or not (1)—with fac- Significance tors including mindlessness, motivation, resource allocation, and arousal (2). Functional MRI (fMRI) studies in humans have linked these Sustained attention varies across people and fluctuates over ’ moment-to-moment attention fluctuations to ongoing activity in time. Patterns of functional brain connectivity predict a person s large-scale brain networks, including the default mode, dorsal overall sustained attention ability, but do they predict changes in attention, and salience networks (3–8). A growing body of work attentional state? Here, across five studies, we show that the has also related changes in functional connectivity measured with same functional connections that predict overall sustained fMRI and intracranial electroencephalography to changes in attention ability predict attention changes observed over mi- attentional and cognitive states (9–14). (Functional connectivity nutes, days, weeks, and months. Furthermore, these functional is measured as the statistical dependence between neuroimaging- connections are sensitive to cognitive and attentional state signal time series in spatially distinct brain regions.) Functional changes induced by anesthesia. Thus, fluctuations in the same connectivity changes have also been related to changing states of functional connections that predict attention in part reflect consciousness (15–17). The degree to which functional connectivity fluctuations in attentional state. dynamics reflect cognitive state dynamics rather than physiological – Author contributions: M.D.R., D.S., R.T.C., and M.M.C. designed research; M.D.R., A.S.G., and measurement noise, however, is still debated (18 22). Fur- E.W.A., Y.H.K., R.R., and M.Q. performed research; D.S. and E.S.F. contributed new re- thermore, despite these advances, cognitive neuroscience lacks a agents/analytic tools; M.D.R. analyzed data; and M.D.R. wrote the paper with comprehensive, quantitative measure of intraindividual differences contributions from all authors. in sustained attention, or changes in attention over time. The authors declare no competing interest. In contrast to the discussions on functional connectivity dy- This article is a PNAS Direct Submission. namics, there is growing consensus that models based on individ- Published under the PNAS license. ’ uals unique patterns of static functional brain connectivity (i.e., Data deposition: The data reported in this paper for Experiment 2 have been deposited in their functional connectome) can predict individual differences the National Institute of Mental Health Data Archive at https://nda.nih.gov/ in abilities, including fluid intelligence (23, 24), working memory edit_collection.html?id=2402. (25–27), and attention (28–32). Static functional connectivity 1To whom correspondence may be addressed. Email: [email protected]. differs from dynamic functional connectivity in that it provides a First published February 4, 2020. www.pnas.org/cgi/doi/10.1073/pnas.1912226117 PNAS | February 18, 2020 | vol. 117 | no. 7 | 3797–3807 Downloaded by guest on September 29, 2021 attention network strength mirror changes in attentional state, and matrices from volumes acquired during individual 3-min task it remains an open question whether the same functional networks blocks, and up to 9 rest-break matrices using volumes acquired that predict differences in attention between people also predict during 32-s rest breaks. Next, using leave-one-subject-out cross- differences in attention within a single person over time. validation, connectome-based models were trained to predict d′ Here, in a series of experiments, we ask whether the using n − 1 participants’ overall task matrices. In every round of sustained attention CPM predicts a person’s attention task cross-validation, the model was applied to each of the held-out performance—above and beyond predicting their overall level of individual’s task-block matrices to generate block-specific d′ pre- sustained attention function—during short experimental blocks dictions. This prediction pipeline replicated that of ref. 33, except and fMRI sessions spread across days, weeks, and months. Fur- that models were applied to the held-out participant’s task-block thermore,weevaluatethemodel’s sensitivity to cognitive and matrices rather than to their overall task matrix (Methods). attentional state changes resulting from pharmacological in- Previous work confirmed that head motion is not significantly terventions by comparing task-free functional connectivity be- correlated with d′ across individuals in this sample (ref. 33 and fore and after the administration of two anesthetics, propofol Methods). However, there is a moderate within-subject relation- and sevoflurane, with different mechanisms of action (for re- ship between mean frame-to-frame head motion and d′ across task views, see refs. 39 and 40). Our results replicate findings that blocks (mean within-subject rs = −0.31). Thus, the performance of the sustained attention CPM generalizes to novel