TY - JOUR
T1 - Dissociable effects of methylphenidate, atomoxetine and placebo on regional cerebral blood flow in healthy volunteers at rest
T2 - A multi-class pattern recognition approach
AU - Marquand, Andre
AU - O'Daly, Owen G.
AU - De Simoni, Sara
AU - Alsop, David C.
AU - Maguire, R. Paul
AU - Williams, Steven C. R.
AU - Zelaya, Fernando O.
AU - Mehta, Mitul A.
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2012/4/2
Y1 - 2012/4/2
N2 - The stimulant drug methylphenidate (MPH) and the non-stimulant drug atomoxetine (ATX) are both widely used for the treatment of attention deficit/hyperactivity disorder (ADHD), but their differential effects on human brain function are poorly understood. PET and blood oxygen level dependent (BOLD) fMRI have been used to study the effects of MPH and BOLD fMRI is beginning to be used to delineate the effects of MPH and ATX in the context of cognitive tasks. The BOLD signal is a proxy for neuronal activity and is dependent on three physiological parameters: regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen and cerebral blood volume. To identify areas sensitive to MPH and ATX and assist interpretation of BOLD studies in healthy volunteers and ADHD patients, it is therefore of interest to characterize the effects of these drugs on rCBF. In this study, we used arterial spin labeling (ASL) MRI to measure rCBF non-invasively in healthy volunteers after administration of MPH, ATX or placebo. We employed multi-class pattern recognition (PR) to discriminate the neuronal effects of the drugs, which accurately discriminated all drug conditions from one another and provided activity patterns that precisely localized discriminating brain regions. We showed common and differential effects in cortical and subcortical brain regions. The clearest differential effects were observed in four regions: (i) in the caudate body where MPH but not ATX increased rCBF, (ii) in the midbrain/substantia nigra and (iii) thalamus where MPH increased and ATX decreased rCBF plus (iv) a large region of cerebellar cortex where ATX increased rCBF relative to MPH. Our results demonstrate that combining ASL and PR yields a sensitive method for detecting the effects of these drugs and provides insights into the regional distribution of brain networks potentially modulated by these compounds.
AB - The stimulant drug methylphenidate (MPH) and the non-stimulant drug atomoxetine (ATX) are both widely used for the treatment of attention deficit/hyperactivity disorder (ADHD), but their differential effects on human brain function are poorly understood. PET and blood oxygen level dependent (BOLD) fMRI have been used to study the effects of MPH and BOLD fMRI is beginning to be used to delineate the effects of MPH and ATX in the context of cognitive tasks. The BOLD signal is a proxy for neuronal activity and is dependent on three physiological parameters: regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen and cerebral blood volume. To identify areas sensitive to MPH and ATX and assist interpretation of BOLD studies in healthy volunteers and ADHD patients, it is therefore of interest to characterize the effects of these drugs on rCBF. In this study, we used arterial spin labeling (ASL) MRI to measure rCBF non-invasively in healthy volunteers after administration of MPH, ATX or placebo. We employed multi-class pattern recognition (PR) to discriminate the neuronal effects of the drugs, which accurately discriminated all drug conditions from one another and provided activity patterns that precisely localized discriminating brain regions. We showed common and differential effects in cortical and subcortical brain regions. The clearest differential effects were observed in four regions: (i) in the caudate body where MPH but not ATX increased rCBF, (ii) in the midbrain/substantia nigra and (iii) thalamus where MPH increased and ATX decreased rCBF plus (iv) a large region of cerebellar cortex where ATX increased rCBF relative to MPH. Our results demonstrate that combining ASL and PR yields a sensitive method for detecting the effects of these drugs and provides insights into the regional distribution of brain networks potentially modulated by these compounds.
KW - HUMAN BRAIN
KW - ENDOGENOUS DOPAMINE
KW - PARKINSONS-DISEASE
KW - Methylphenidate
KW - Atomoxetine
KW - ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
KW - Multi-class pattern recognition
KW - FUNCTIONAL MAGNETIC-RESONANCE
KW - Arterial spin labeling
KW - NOREPINEPHRINE TRANSPORTERS
KW - DEFICIT HYPERACTIVITY DISORDER
KW - SUPPORT VECTOR MACHINES
KW - LOGISTIC-REGRESSION
KW - DOPAMINE TRANSPORTER
UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-84863406628&md5=7d74c4aba8ea773680699e07ff8e7d47
U2 - 10.1016/j.neuroimage.2012.01.058
DO - 10.1016/j.neuroimage.2012.01.058
M3 - Article
C2 - 22266414
SN - 1095-9572
VL - 60
SP - 1015
EP - 1024
JO - NeuroImage
JF - NeuroImage
IS - 2
ER -
