title: The Effects of Methylphenidate on Resting-State Functional Connectivity of the Basal Nucleus of Meynert, Locus Coeruleus, and Ventral Tegmental Area in Healthy Adults.
abstract: BACKGROUND
  Methylphenidate (MPH) influences catecholaminergic signaling. Extant work examined the effects of MPH on the neural circuits of attention and cognitive control, but few studies have investigated the effect of MPH on the brain's resting-state functional connectivity (rsFC).
  
  
  METHODS
  In this observational study, we compared rsFC of a group of 24 healthy adults who were administered an oral 45 mg dose of MPH with a group of 24 age and gender matched controls who did not receive MPH. We focused on three seed regions: basal nucleus of Meynert (BNM), locus coeruleus (LC), and ventral tegmental area/substantia nigra, pars compacta (VTA/SNc), each providing cholinergic, noradrenergic and dopaminergic inputs to the cerebral cortex. Images were pre-processed and analyzed as in our recent work (Li et al., 2014; Zhang et al., 2015). We used one-sample t-test to characterize group-specific rsFC of each seed region and two-sample t-test to compare rsFC between groups.
  
  
  RESULTS
  MPH reversed negative connectivity between BNM and precentral gyri. MPH reduced positive connectivity between LC and cerebellum, and induced positive connectivity between LC and right hippocampus. MPH decreased positive VTA/SNc connectivity to the cerebellum and putamen, and reduced negative connectivity to left middle occipital gyrus.
  
  
  CONCLUSIONS
  MPH had distinct effects on the rsFC of BNM, LC, and VTA/SNc in healthy adults. These new findings may further our understanding of the role of catecholaminergic signaling in Attention Deficit Hyperactivity Disorder (ADHD) and Parkinson's disease and provide insights into the therapeutic mechanisms of MPH in the treatment of clinical conditions that implicate catecholaminergic dysfunction.
authors.affiliation: Department of Psychology, Yale University School of Arts and Sciences New Haven, CT, USA.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Kline
authors.affiliation: Department of Psychiatry, Yale University School of Medicine New Haven, CT, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Interdepartmental Neuroscience Program, Yale University New Haven, CT, USA.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Farr
authors.affiliation: Department of Psychiatry, Yale University School of Medicine New Haven, CT, USA.
authors.forename: Sien
authors.initials: S
authors.lastname: Hu
authors.affiliation: Center for Molecular and Behavioral Neuroscience Rutgers, NJ, USA.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Zaborszky
authors.affiliation: Department of Psychology, Yale University School of Arts and SciencesNew Haven, CT, USA; Interdepartmental Neuroscience Program, Yale UniversityNew Haven, CT, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Samanez-Larkin
authors.affiliation: Department of Psychiatry, Yale University School of MedicineNew Haven, CT, USA; Interdepartmental Neuroscience Program, Yale UniversityNew Haven, CT, USA; Department of Neurobiology, Yale University School of MedicineNew Haven, CT, USA.
authors.forename: Chiang-Shan R
authors.initials: CS
authors.lastname: Li
keywords: BOLD; acetylcholine; basal forebrain; dopamine; midbrain; norephinephrine; resting state connectivity