The synergy of working memory and inhibitory control: Behavioral, pharmacological and neural functional evidences
Neurobiology of Learning and Memory. 2012-02-01; 97(2): 202-212
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1. Neurobiol Learn Mem. 2012 Feb;97(2):202-12. doi: 10.1016/j.nlm.2011.12.003. Epub
2011 Dec 16.
The synergy of working memory and inhibitory control: behavioral, pharmacological
and neural functional evidences.
Grégoire S(1), Rivalan M, Le Moine C, Dellu-Hagedorn F.
(1)CNRS, INCIA, UMR 5287, F-33000 Bordeaux, France; Univ. Bordeaux, INCIA, UMR
5287, F-33000 Bordeaux, France.
Concomitant deficits in working memory and behavioral inhibition in several
psychiatric disorders like attention-deficit/hyperactivity disorder, addiction or
mania, suggest that common brain mechanisms may underlie their etiologies. Based
on the theoretical assumption that a continuum exists between health and mental
disorders, we explored the relationship between working memory and inhibition in
healthy individuals, through spontaneous inter individual differences in
behavior, and tested the hypothesis of a functional link through the
fronto-striatal dopaminergic system. Rats were classified into three groups,
showing good, intermediate and poor working memory and were compared for their
inhibitory abilities. These two functions were simultaneously modulated by a
dose-effect of d-amphetamine and in situ hybridization was used to quantify
dopaminergic receptor (RD1) mRNAs in prefrontal cortex and striatal areas. A
functional relationship between working memory and inhibition abilities was
revealed. Both functions were similarly modulated by d-amphetamine according to
an inverted-U shaped relationship and depending on initial individual
performances. D-amphetamine selectively improved working memory and inhibition of
poor and intermediate performers at low doses whereas it impaired both processes
in good performers at a higher dose. D1 receptors were less expressed in
prelimbic, infralimbic and anterior cingulate cortices of good compared to
intermediate and poor performers, whereas no difference was observed between
groups in striatal areas. The synergy of working memory and inhibitory abilities,
observed in both healthy and psychiatric populations, may originate from
endogenous variability in dopaminergic prefrontal cortex activity. Such findings
confirm the validity of a dimensional approach, based on the concept of
continuity between health and mental disorders for identifying endophenotypes of
Copyright © 2011 Elsevier Inc. All rights reserved.
PMID: 22197651 [Indexed for MEDLINE]