title: Methylphenidate Modulates Functional Network Connectivity to Enhance Attention.
abstract: Recent work has demonstrated that human whole-brain functional connectivity patterns measured with fMRI contain information about cognitive abilities, including sustained attention. To derive behavioral predictions from connectivity patterns, our group developed a connectome-based predictive modeling (CPM) approach (Finn et al., 2015; Rosenberg et al., 2016). Previously using CPM, we defined a high-attention network, comprising connections positively correlated with performance on a sustained attention task, and a low-attention network, comprising connections negatively correlated with performance. Validating the networks as generalizable biomarkers of attention, models based on network strength at rest predicted attention-deficit/hyperactivity disorder (ADHD) symptoms in an independent group of individuals (Rosenberg et al., 2016). To investigate whether these networks play a causal role in attention, here we examined their strength in healthy adults given methylphenidate (Ritalin), a common ADHD treatment, compared with unmedicated controls. As predicted, individuals given methylphenidate showed patterns of connectivity associated with better sustained attention: higher high-attention and lower low-attention network strength than controls. There was significant overlap between the high-attention network and a network with greater strength in the methylphenidate group, and between the low-attention network and a network with greater strength in the control group. Network strength also predicted behavior on a stop-signal task, such that participants with higher go response rates showed higher high-attention and lower low-attention network strength. These results suggest that methylphenidate acts by modulating functional brain networks related to sustained attention, and that changing whole-brain connectivity patterns may help improve attention.
  
  
  
  Recent work identified a promising neuromarker of sustained attention based on whole-brain functional connectivity networks. To investigate the causal role of these networks in attention, we examined their response to a dose of methylphenidate, a common and effective treatment for attention-deficit/hyperactivity disorder, in healthy adults. As predicted, individuals on methylphenidate showed connectivity signatures of better sustained attention: higher high-attention and lower low-attention network strength than controls. These results suggest that methylphenidate acts by modulating strength in functional brain networks related to attention, and that changing whole-brain connectivity patterns may improve attention.
authors.affiliation: Department of Psychology, monica.rosenberg@yale.edu.
authors.forename: Monica D
authors.identifier: 0000-0001-6179-4025
authors.initials: MD
authors.lastname: Rosenberg
authors.affiliation: Departments of Psychiatry.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Psychology, Yale College, and.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hsu
authors.affiliation: Radiology and Biomedical Imaging, Yale School of Medicine, Yale University, New Haven, Connecticut 06520.
authors.forename: Dustin
authors.initials: D
authors.lastname: Scheinost
authors.affiliation: Interdepartmental Neuroscience Program.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Finn
authors.affiliation: Radiology and Biomedical Imaging, Yale School of Medicine, Yale University, New Haven, Connecticut 06520.
authors.forename: Xilin
authors.initials: X
authors.lastname: Shen
authors.affiliation: Interdepartmental Neuroscience Program, Neurosurgery, Radiology and Biomedical Imaging, Yale School of Medicine, Yale University, New Haven, Connecticut 06520.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Constable
authors.affiliation: Interdepartmental Neuroscience Program, Departments of Psychiatry, Neuroscience, and.
authors.forename: Chiang-Shan R
authors.identifier: 0000-0002-9393-1212
authors.initials: CS
authors.lastname: Li
authors.affiliation: Department of Psychology, Interdepartmental Neuroscience Program, Neuroscience, and.
authors.forename: Marvin M
authors.identifier: 0000-0003-1070-7993
authors.initials: MM
authors.lastname: Chun
mesh_terms: D000328:Adult; D001288:Attention / Q000187:drug effects*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D063132:Connectome; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009434:Neural Pathways / Q000000981:diagnostic imaging* / Q000187:drug effects; D009483:Neuropsychological Tests; D011930:Reaction Time / Q000187:drug effects; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate
keywords: fMRI; functional connectivity; methylphenidate; neuromarker; predictive marker; sustained attention