Some early uses of the concept are found at least by 1861, when

Gratiolet referred to the frontal lobes as the site of the “regulating mind” or the “supreme organ of the brain.”1 Luria also credits Broadbent2,3 and Jackson4,5 with early development of concepts regarding the importance of the frontal lobes In the hierarchical regulation of behavior. The actual use of the term “executive function” to refer to frontal lobe function has been credited Inhibitors,research,lifescience,medical to Karl Pribram, who wrote In 1973: “ the frontal cortex appears critically involved in implementing executive programs when these are necessary to maintain brain organization in the face of insufficient redundancy in input processing and in the outcomes of behavior”6 (p 312). Pribram’s usage here was tied to then-current computer terminology referring to “flexible noticing order programs” that were applied in the sequencing and tracking Inhibitors,research,lifescience,medical of routines in a context-sensitive manner, and in this way he distinguished such control

processes from strictly hierarchical programs which are context-free. The term “working memory” (a coinage Inhibitors,research,lifescience,medical attributed to Miller, Galanter, and Pribram7) developed its own niche role as one of the components of “executive function.” This may be attributed at least in part to the widespread uptake of the term in cognitive psychology following its use in influential works by Alan Baddeley and colleagues.8 Many of these cognitive works assiduously avoided attributions to specific brain mechanisms, despite knowledge that the frontal lobes were critical for delayed response task performance.9 Later experiments provided Inhibitors,research,lifescience,medical considerably greater detail about the specific nature of the deficit produced by frontal versus high throughput screening compounds posterior cortical lesions on these behaviors,

documenting firing patterns of prefrontal pyramidal Inhibitors,research,lifescience,medical cells during delay periods, and using selective lesions to reveal the roles of reciprocal connections between frontal and posterior cortical regions, the relations of these transmissions to graded electrical potential changes over relevant cortical or scalp regions (reviewed by Pribram and McGuinness10,11), and then linking these sustained activation most patterns to specific pharmacological manipulations, particularly of dopamine (DA) neurons.12-13 Today this work has progressed to include biophysically detailed models of mechanisms responsible for stabilizing and introducing flexibility into sustained activation states of these neural networks.14-16 To highlight how construct labels may impact science, however, it is exemplary to consider what happened to the term “executive functions” in the project – Measurement and Treatment Research to Improve Cognition In Schizophrenia (MATRICS).