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| Research article summary (published 29 Jun 2003): |
A novel method for noninvasive detection of neuromodulatory changes in specific neurotransmitter systems.
Full Abstract
Over the last decade, it has become possible to study theories of cognition using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). These methods yield statistical parametric maps of changes in cerebral blood flow (CBF) elicited by cognitive tasks. A limitation of these studies is that they provide no information about the underlying neurochemistry. However, it is possible to extend the concept of activation studies to include measurements targeting neurotransmitters and specific receptor populations. Cognitive activation increases neuronal firing rate, increasing the endogenous neurotransmitter level. The increased neurotransmitter level can be used to alter the kinetics of specifically bound radioligands. We describe a new approach to the design and analysis of neuromodulation experiments. This approach uses PET, a single-scan session design, and a linear extension of the simplified reference region model (LSSRM) that accounts for changes in ligand binding induced by cognitive tasks or drug challenge. In the LSSRM, an "activation" parameter is included that represents the presence or absence of change in apparent dissociation rate. Activation of the neurotransmitter is detected statistically when the activation parameter is shown to violate the null hypothesis. Simulation was used to explore the properties of the LSSRM with regard to model identifiability, effect of statistical noise, and confounding effects of CBF-related changes. Simulation predicted that it is possible to detect and map neuromodulatory changes in single-subject designs. A human study was conducted to confirm the predictions of simulation using (11)C-raclopride and a motor planning task. Parametric images of transport, binding potential, areas of significant dopamine release, and statistical parameters were computed. Examination of the kinetics of activation demonstrated that maximum dopamine release occurred immediately following task initiation and then decreased with a half-time of about 3 min. This method can be extended to explore neurotransmitter involvement in other behavioral and cognitive domains.
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Author information
Author/s: Alpert, Nathaniel M (NM); Badgaiyan, Rajendra D (RD); Livni, Elijahu (E); Fischman, Alan J (AJ);
Affiliation: Division of Nuclear Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. alpert(-atsign-)pet.mgh.harvard.edu
Grants: T32CA09362 (Agency:United States NCI)
Journal and publication information
Publication Type: Clinical Trial; Journal Article; Research Support, U.S. Gov't, P.H.S.
Journal: NeuroImage (Neuroimage), published in United States. (Language: eng)
Reference: 2003-Jul; vol 19 (issue 3) : pp 1049-60
Dates: Created 2003/07/25; Completed 2003/09/09; Revised 2007/11/14;
PMID: 12880831, status: MEDLINE (last retrieval date: 11/6/2008)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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